Dissertations / Theses: 'Arthriti'

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Bellan, Mattia. "Vitamin D in Rheumatoid Arthritis: potential implications for disease control and comorbidities management." Doctoral thesis, Università del Piemonte Orientale, 2018. http://hdl.handle.net/11579/102686.

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Background. Vitamin D is able to regulate the activity of immune system in vitro; whether this action has some relevance in vivo is still a matter of debate. Aim. To investigate the potential role of vitamin D in the pathogenesis and in the management of Rheumatoid Arthritis (RA) and its comorbidities, in particular insulin resistance. Methods. We investigated the expression of tha main target genes implicated in vitami D metabolism on synovial samples obtained from RA and Osteoarthritis (OA) patients; moreover, we evaluated the expression of the CYP27B1, the activating enzyme of vitamin D metabolism, by synovial fibroblasts (SF) of RA patients in vitro. We also investigated, in vivo, the relevance of visceral obesity, assessed by ultrasounds, in the prediction of cardiovascular risk and glucose metabolism in the general population. Finally, we evaluated the cross-sectional association between glucose metabolism parameters and vitamin D plasma concentration in severely obese diabetic subjects. Results. In the present study we failed to demonstrate significant differences in vitamin D metabolism between RA and OA patients; however, we demonstrated that SF express CYP27B1 under inflammatory state, being potentially able to locally activate vitamin D. Moreover we confirmed that visceral obesity, a well known risk factor for hypovitaminosis D, is the main determinant of insulin resistance and is a strong predictor of cardiovascular risk. Finally, we demonstrated that vitamin D in severely obese type 2 diabetes mellitus patients predicts glycemic control. Conclusions. Our data support the hypothesis that the local conversion of vitamin D could be exploited for therapeutic use in RA; finally, the improvement of vitamin D status might have beneficial effects on different comorbidities related to RA, in particular insulin resistance.

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RAVANI, Annalisa. "Pharmacological characterization of adenosine receptors in chronic inflammatory rheumatic diseases." Doctoral thesis, Università degli studi di Ferrara, 2018. http://hdl.handle.net/11392/2478762.

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L’artrite reumatoide, la spondilite anchilosante e l’artrite psoriasica sono malattie infiammatorie croniche, progressive e invalidanti che colpiscono le articolazioni provocando dolore e disabilità. I recettori dell’adenosina giocano un ruolo fondamentale nel meccanismo infiammatorio, in particolare l’attivazione dei sottotipi recettoriali A2A e A3 è spesso associata ad una riduzione dello stato infiammatorio. Il primo obiettivo di questo studio è stato quello di indagare il coinvolgimento dei recettori adenosinici nei pazienti affetti da artrite reumatoide all’esordio della patologia (non ancora in cura), artrite reumatoide, spondilite anchilosante ed artrite psoriasica. L’analisi dell’RNA messaggero (mRNA) e gli esperimenti di saturazione del binding hanno indicato una sovraespressione dei recettori A2A e A3 dell’adenosina nei linfociti ottenuti dai pazienti, comparati con soggetti di controllo sani. Gli agonisti dei recettori adenosinici A2A e A3 sono stati in grado di inibire l’attivazione di NF-κB, un complesso proteico funzionante come fattore di trascrizione. Inoltre hanno ridotto il rilascio di citochine pro infiammatorie, come ad esempio TNF-α, IL-1β e IL-6. Per di più l’attivazione dei sottotipi recettoriali A2A e A3 è stata in grado di mediare una riduzione delle metalloproteasi (MMP)-1 e MMP-3. L’effetto degli agonisti è stato annullato grazie alla somministrazione di antagonisti recettoriali selettivi, dimostrando così il diretto coinvolgimento di questi sottotipi recettoriali. Questi dati confermano l’implicazione dei recettori dell’adenosina nelle patologie reumatiche cronico degenerative evidenziando la possibilità di utilizzare i recettori A2A e A3 dell’adenosina come target terapeutici, con lo scopo di limitare la risposta infiammatoria spesso associata ad artrite reumatoide, spondilite anchilosante ed artrite psoriasica. Lo scopo del secondo capitolo di questa tesi, è stato quello di valutare la modulazione dei recettori A2A e A3 dell’adenosina nei pazienti affetti dalle patologie prese in esame nel primo capitolo, dopo diversi trattamenti farmacologici. Abbiamo indagato sulla densità e la funzionalità recettoriale nella progressione delle patologie attraverso uno studio longitudinale nei pazienti affetti da artrite reumatoide, spondilite anchilosante ed artrite psoriasica prima e dopo le terapie in uso, quali metotressato, agenti anti-TNFα o rituximab. I recettori A2A e A3 dell’adenosina sono stati analizzati attraverso esperimenti di saturazione del binding nei linfociti dei pazienti presi in esame, durante un periodo di ricerca della durata di 24 mesi. Nei linfociti ottenuti dai pazienti affetti da artrite reumatoide, la sovraespressione dei sottotipi recettoriali A2A e A3 dell’adenosina è stata gradualmente ridotta in funzione del tempo di trattamento. Questi risultati confermano il coinvolgimento dei recettori adenosinici A2A e A3 nella progressione delle patologie reumatiche cronico degenerative, sottolineando che gli agonisti dei recettori A2A e A3 dell’adenosina potrebbero rappresentare un’alternativa terapeutica per il trattamento dell’artrite reumatoide.
Rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) are chronic inflammatory rheumatic diseases that affect joints, causing debilitating pain and disability. Adenosine receptors (ARs) play a key role in the mechanism of inflammation, and the activation of A2A and A3AR subtypes is often associated with a reduction of the inflammatory status. The first aim of this study was to investigate the involvement of ARs in patients suffering from early-RA (ERA), RA, AS and PsA. Messenger RNA (mRNA) analysis and saturation binding experiments indicated an upregulation of A2A and A3ARs in lymphocytes obtained from patients when compared with healthy subjects. A2A and A3AR agonists inhibited nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) activation and reduced inflammatory cytokines release, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6. Moreover, A2A and A3AR activation mediated a reduction of metalloproteinases (MMP)-1 and MMP-3. The effect of the agonists was abrogated by selective antagonists demonstrating the direct involvement of these receptor subtypes. These data confirmed the involvement of ARs in chronic autoimmune rheumatic diseases highlighting the possibility to exploit A2A and A3ARs as therapeutic targets, with the aim to limit the inflammatory responses usually associated with RA, AS and PsA. The purpose of the second chapter of this thesis, was to evaluate the modulation of A2A and A3ARs in patients suffering from RA, AS and PsA after different pharmacological treatments. We investigated A2A and A3AR density and functionality in pathologies progression by using a longitudinal study in RA, AS and PsA patients before and after methotrexate (MTX), anti-TNFa agents or rituximab treatments. A2A and A3ARs were analyzed by saturation binding assays in lymphocytes from patients throughout the 24-month study timeframe. In lymphocytes obtained from RA patients, the A2A and A3AR up-regulation was gradually reduced in function of the treatment time. Taken together, these data confirmed the involvement of A2A and A3ARs in chronic inflammatory rheumatic disease progression and highlighted that A2A and A3AR agonists could represent a physiological-like therapeutic alternative for RA treatment.

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SILVAGNI, ETTORE. "Tofacitinib improves mitochondrial function in psoriatic arthritis fibroblast-like synoviocytes via autophagy modulation." Doctoral thesis, Università degli studi di Ferrara, 2022. http://hdl.handle.net/11392/2482880.

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Psoriatic arthritis (PsA) is a chronic inflammatory systemic disease, and peripheral joints involvement is responsible of significant morbidity for patients, leading to damage accrual. Different drugs are available for the systemic management of this condition, with different mechanisms of action. Nevertheless, the rules driving the correct therapeutical choice in each individual patient are not completely defined. Janus kinases (JAK) inhibitors are a class of drugs able to reduce synovial inflammation in patients, and tofacitinib, a JAK1/3 inhibitor, is the most studied. Preliminary evidence suggest an effect of tofacitinib on fibroblast-like synoviocytes (FLS), reducing pro-invasive and pro-inflammatory properties, as well as improving mitochondrial function. The link between JAK inhibition and mitochondrial function improvement at synovial level is not completely understood. Materials and Methods: This is an in vitro study. Patients with active PsA underwent ultrasound-guided synovial biopsy in the context of a tertiary-referral outpatient clinic. Histological evaluation was performed according to Krenn’s synovitis score. FLS, peripheral blood mononuclear cells (PBMCs), and synovial explants cultures were set up, and cells were treated in vitro with tofacitinib 1 µM or vehicle control for 24h. For some experiments, the autophagy-inducer rapamycin was utilized, as well. Protein levels in cellular homogenates were analysed by western blot for relevant autophagy markers, and chemokines/cytokines into culture supernatants were quantified by ELISA. Migration assays were used to investigate the effect of tofacitinib on invasive properties of FLS, while specific mitochondrial probes were used to measure intracellular reactive oxygen species (ROS), mitochondrial potential, and mitophagy. Oxygen consumption rate (OCR), reflecting oxidative phosphorylation, was quantified using the Seahorse technology. Differences were determined adopting the non-parametric Wilcoxon signed rank test. Results: 16 patients with moderately active PsA were enrolled. Mean (SD) Krenn’s synovitis score was 4.4. (1.9). Tofacitinib significantly increased LC3-II (p=0.0002) and ATG7 (p=0.0001) levels in PsA FLS compared to vehicle control, suggesting an increase in spontaneous autophagy activity. No effect was highlighted in PBMCs and synovial explants cultures. Tofacitinib reduced migration properties of PsA FLS (p=0.0024), and a similar trend was documented using rapamycin. Moreover, tofacitinib reduced MCP-1 and IL-6 release into FLS supernatants (p=0.0007 and p=0.0022, respectively), reduced intracellular ROS production (p=0.0180), increased basal OCR (p=0.02809), ATP production (p=0.0280) and maximal respiratory capacity (p=0.0180), and enhanced mitophagy (p=0.0156). Conclusion: The JAK inhibitor tofacitinib reduces pro-invasive and pro-inflammatory properties of PsA FLS and improves mitochondrial function. The induction of autophagy/mitophagy by tofacitinib might permit the removal of damaged mitochondria and a better functioning of the remaining ones.

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Innala, Lena. "Early rheumatoid arthritis aspects of severity and co-morbidity." Doctoral thesis, Umeå universitet, Reumatologi, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-88477.

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Background Rheumatoid arthritis (RA) is a systemic progressive destructive joint disease with an increased risk for co-morbidity and premature death if untreated. Cardiovascular disease (CVD) is the main cause of death but also other co-morbid conditions contribute to the patient’s shorter life expectancy. Inflammation is important for the development of CVD, but knowledge of its relationship with other co-morbidities is sparse. Early disease modifying anti rheumatic drugs (DMARDs) can suppress disease activity and improve the long-term outcome. The aim of this thesis was to evaluate prospectively aspects of disease activity and severity in a large cohort of patients with early RA. Predictive and prognostic markers, e.g., antibodies against citrullinated proteins/peptides (ACPAs), occurring in early disease and with implications for disease outcome and co-morbidity were evaluated. Methods Patients with early RA (i.e., symptomatic for ≤12 months) have, since December 1995, been consecutively included in a large survey of prospective and observational studies on the progression of RA and the development of co-omorbidity. Autoantibodies, inflammatory, genetic markers and radiographs have been analyzed. In paper I, 210 RA patients and 102 controls were followed regularly for two years. The predictive value of four different ACPAs in relation to disease activity and radiological progression was evaluated. In Paper II (n = 700) and in Papers III-IV (n =950), patients with early RA from the four northern-most counties of Sweden were followed regularly for 5 years. Data on risk factors and co-morbidity was collected, according to the study protocol, from clinical records and self-reported questionnaires from patients at inclusion into the study cohort and after five years. The predictive value of traditional and potential disease related risk factors for new cardiovascular events (CVE) was evaluated (II). In Paper III, the impact of age at the onset RA, stratified as being young onset RA (<58 years; YORA) and late onset RA (≥58 years; LORA) on disease activity, severity and chosen treatment, was evaluated. In Paper IV, the development of new co-morbidities after RA onset and their relation to inflammatory activity was assessed. Results The presence of anti-mutated citrullinated vimentin (MCV ) antibodies was associated with a more severe disease course, estimated by disease activity score, erythrocyte sedimentation rate (ESR) and swollen joint count after 24 months, compared with anti-CCP2, anti-CCP3, and anti CCP3.1 antibodies. In Paper II, the incidence of a new CVE during 5 years was explained by several of the traditional CV risk factors, and potentiated by a high disease activity. Treatment with DMARDs decreased the risk. In Paper III, LORA patients were associated with greater disease activity/severity at disease onset and over time compared with YORA who were more often ACPA positive. YORA patients were treated earlier with DMARDs, whilst LORA patients were more often treated with corticosteroids and less so with DMARDs early in the course of their disease. In Paper IV, 53%of patients already had one or more co-morbidities already at the onset of RA. After 5 years, 41% of the patients had developed at least one new co-morbidity. ESR at baseline and accumulated disease activity were associated with a new co-morbidity after five years. Conclusion Early RA patients sero-positive for anti- MCV antibodies appeared to have a higher disease activity over time. The occurrence of a new CVE in early RA patients was predicted by traditional risk factors for CVD which were potentiated by a high disease activity. Treatment with DMARDs decreased the risk. Patients with young onset of RA were associated with a higher frequency of ACPA. Late onset of RA was associated with higher disease activity/severity at inclusion and over time. However, LORA patients were more often treated with corticosteroids and less so with DMARDs early in the disease course. Development of a new co-morbidity during the five years following diagnosis was related to ESR.

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BASSI, ANDREASI Rita. "MULTIDISCIPLINARY APPROACHES AND INTERACTION NETWORK IN THE DIAGNOSIS AND TREATMENT OF RHEUMATOID ARTHRITIS." Doctoral thesis, Università degli studi di Ferrara, 2018. http://hdl.handle.net/11392/2488115.

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The multidisciplinary approaches described and reported in the present thesis were performed with the aim to gain new insight into Rheumatoid Arthritis (RA), multifactorial, progressive and autoimmune disease. The case-control study, focused on the genetic occurrence risk of RA in a complete Italian casuistry, reported the HLA-DQA2 rs9275595 T>C variant strongest associated to RA susceptibility. SNP × SNP investigation revealed significant synergic combined effect between HLA-DQA2 rs9275595 and HLA-DRB1 rs660895 A>G variants, suggesting that, beyond single variant association, the powerful gain arises from interaction between variants belonging to HLA complex. The predictive biomarkers identification of occurrence, progression and therapy efficacy has been carried out in Undifferentiated Arthritis/ Early Rheumatoid Arthritis patients (UA/ERA). Follow-up after 6 months from the first visit has allowed to stratify subjects accordingly to disease evolution (from UA to RA) and to disease progression (from ERA to RA) using DAS28 variation (Disease Activity Score). Interaction study between genetics and serological parameters reported a significant combined effect of Rheumatoid Factor (RF), resistin and HLA-DRB1 rs6910071 A>G, playing a role together to predict "best responders", the group of patients with higher DAS28 improvement. Focusing on the influence of sexual dimorphism, a statistical significant gender-dependent effect has been shown in the context of Methtotrexate (MTX) pharmacogenetics: RA women D/I for HLA-G 14bp D>I variant reported significant higher MTX inefficacy, whereas male trend of association was completely opposite. Investigating on women previous obstetric history, it came out the association between the ascertained pregnancies, HLA-G 14bp D/I genotype and MTX inefficacy. Thus, we focused the approach on the particular women-view, underlying how pregnancy and miscarriage could exert an important and discriminant role in the disease pathogenesis. Pregnancy represents a physiological context requiring immune tolerance toward the fetus and, especially during the first trimester, exists a bidirectional trafficking of cells and DNA in the fetus-maternal interface that can results in naturally acquired microchimerism in both mother (fMC) and fetus. Male fMC could be detected in women bloodstream even after many years from the childbirth and in fact, our findings revealed the presence of male fMC in SLE patients' bloodstream. The widespread symptoms of SLE could justify the higher presence of fMC than which has detected in RA patients' bloodstream and the investigation on localized RA affected synovium might be crucial to understating fMC role. Exploring women synovial biopsies, it failed to reveal positive detection of fMC, empathizing that microchimeric cells can exert a rescue role, acting as stem cells repairing tissues injuries; thus, it has possible to detect fMC cells only in slight or mild RA cases. Finally, we explored the epigenetic profile, through the methylation analysis of LINE-1 and of specific genes HLA-G and MTHFR. Study has been carried out on healthy subjects, passing through early symptoms, to established RA diseased patients. HLA-G gene was significant hypermethylated in female RA patients, respect to RA males. Significant hypomethylation was identified in MTHFR gene, with a progressive rising to the increase of disease establishment, suggesting that epigenetic state persists beyond RA stages. In conclusion, the evidences presented in this thesis underlined the interaction network as the important causative factor of RA susceptibility and therapy efficacy. In addition, results on RA affected women emphasized the gender medicine application. Lastly, the epigenetic study is the first to explore methylation status over the time and progression of RA disease, highlighting the environmental contribution and opening new directional window in the RA knowledge.
I differenti approcci multidisciplinari affrontati e descritti nella presente tesi sono stati effettuati con l'intento di arricchire le conoscenze in ambito di Artrite Reumatoide (AR), patologia a eziologia multifattoriale, progressiva ed autoimmune. Lo studio caso-controllo, focalizzato sull'individuazione di un profilo genetico di rischio in pazienti italiani con diagnosi di AR, ha riportato la variante HLA-DQA2 rs9275595 T>C significativamente associata ad insorgenza. L'analisi delle interazioni SNP × SNP ha rivelato un significativo effetto sinergico della combinazione fra le varianti HLA-DQA2 rs9275595 e HLA-DRB1 rs660895 A>G, suggerendo che, oltre al singolo effetto, il risultato maggiore si ha dall'interazione fra varianti appartenenti al complesso HLA. L'identificazione di biomarkers predittivi di suscettibilità, di progressione e di efficacia del trattamento impiegato è stata condotta in pazienti con Artrite Indifferenziata/Artrite Reumatoide Precoce (UA/ERA). Il follow-up a 6 mesi ha consentito la stratificazione dei soggetti UA in base all'insorgenza o meno della patologia, mentre per i pazienti ERA in base alla variazione del DAS28 (Disease Activity Score). I risultati delle interazioni genetiche e sierologiche relativamente alla progressione di AR, hanno individuato un algoritmo predittivo di efficacia terapeutica, evidenziando una relazione sinergica fra il Fattore Reumatoide (RF), la Resistina e la variante HLA-DRB1 rs6910071 A>G. Focalizzandosi sullo studio del dimorfismo sessuale, è stato riportato un significativo effetto genere-dipendente nel contesto della farmacogenetica del Methotrexate (MTX): infatti la variante HLA-G 14bp D>I costituisce un fattore predittivo dell'inefficacia del MTX solo nelle pazienti femmine. Approfondendo l'indagine su peculiari caratteristiche del genere femminile che possano interagire con il genotipo HLA-G, è risultata una forte associazione fra la presenza di precedenti gravidanze accertate, il genotipo HLA-G 14bp D/I e l'inefficacia al MTX. Considerando l'elevata espressione di HLA-G a livello del trofoblasto e il suo coinvolgimento nelle poliabortività, è stato indagato il microchimerismo fetale (fMC), già noto per essere presente nel sangue di donne affette da patologie autoimmuni, come AR e Lupus Eritematoso Sistemico (LES), anche dopo molti anni dalla gravidanza o dall'evento abortivo. Lo studio caso-controllo ha rilevato significativa presenza di fMC maschile nel campione ematico periferico di pazienti lupiche. La sintomatologia sistemica di LES potrebbe giustificare l'elevata presenza di fMC maschile nelle pazienti lupiche rispetto alle pazienti AR. Indagando le biopsie sinoviali di donne affette da AR, non è stata rivelata presenza di fMC maschile, suggerendo il possibile ruolo delle cellule microchimeriche come elementi di supporto e di rescue nel miglioramento della patologia. Sarebbe, dunque, possibile individuare cellule fMC solo nei casi di pazienti con AR stabile o in fase di remissione. Infine, è stata esplorato il profilo epigenetico attraverso analisi di metilazione di LINE-1 e dei geni HLA-G e MTHFR, su soggetti sani di controllo, su pazienti con artrite agli esordi e su pazienti con diagnosi accertata di AR. HLA-G ha evidenziato una significativa ipermetilazione nelle pazienti donne con AR rispetto agli uomini; mentre MTHFR ha rivelato una significativa ipometilazione, gradualmente maggiore a seconda della progressione di AR. In conclusione, i risultati esposti nella presente tesi hanno evidenziato il network di interazioni come importante elemento causativo di insorgenza e risposta terapeutica di AR. Inoltre, il focus sulle pazienti donne affette da AR ha enfatizzato l'applicazione della medicina di genere; infine, lo studio di epigenetica è il primo ad indagare lo stato di metilazione e la progressione di AR, sottolineando l'importanza del contributo ambientale e consentendo una nuova direzione esplorativa.

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Riding, S. Barbara. "The arthritic pain experience of children with juvenile rheumatoid arthritis." Thesis, University of British Columbia, 1988. http://hdl.handle.net/2429/27731.

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This study was designed to investigate the experience of having arthritic pain from the children's perspective. Previous research on how Canadian children perceive and manage arthritic pain and how it affects their daily lives is nonexistent. Therefore the purpose of this qualitative descriptive study was to explore and describe the arthritic pain experience of school age children with juvenile rheumatoid arthritis (JRA) and to understand the impact/influence of various factors on the construction of that experience. Ten children, aged 10 to 13 years, with either early (at 2 to 4 years) or late (at 7 to 11 years) onset arthritis participated in this study. Descriptive data were obtained during two open-ended in depth interviews with the children in their homes. Using content analysis, data were analyzed for themes and their elements. An analytical framework of themes and their elements was developed that reflected the children's descriptions of and explanations for arthritic pain in the context of their day to day in the context of their day to day living with arthritis, both in the past and currently. The children perceived pain to be synonymous with arthritis and the mediating factor in how they functioned. They described arthritic pain in relation to distinguishing factors: intensity, duration, and frequency. Intermittent arthritic pain was attributed to cessation of medications, arthritis "flare-ups," inactivity, and activity. A current concern for most children was pain attributed to activity because it meant limitations in activities with peers. The children identified strategies they used to manage pain and cope with pain's unpredictability. The findings of this study were discussed in relation to selected research studies that either supported or refuted the findings of this study. Implications for nursing practice and research were addressed.
Applied Science, Faculty of
Nursing, School of
Graduate

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MAZZONI, MARTA. "VALORE PREDITTIVO DELL’ECOGRAFIA MUSCOLOSCHELETRICA NEI PAZIENTI AFFETTI DA ARTRITE IDIOPATICA GIOVANILE IN REMISSIONE CLINICA." Doctoral thesis, Università degli studi di Genova, 2021. http://hdl.handle.net/11567/1046998.

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Background: the accurate assessment of remission status in JIA patients is of utmost relevance to taper medications and prevent side effects from their long-term administration. In RA patients in clinical remission (CR), musculoskeletal ultrasound (MSUS) allows to detect persistent joint inflammation (subclinical synovitis), which predicts disease flare and structural damage progression. Although subclinical synovitis has been reported in a substantial proportion of JIA patients with inactive disease, its prognostic value is still being defined. Objectives: 1) to investigate the prevalence of MSUS-detected subclinical synovitis in JIA patients in CR; 2) to establish which and how many joints should be scanned to reliably assess remission; 3) to evaluate the persistence of subclinical synovitis over the time; 4) to investigate whether subclinical synovitis entails a risk of disease flare and whether it should affect the therapeutic strategy. Methods: 135 consecutive JIA patients who met the Wallace criteria for CR were included in this 3-years prospective study. All patients underwent MSUS assessment of 56 joints at study entry and at 6 months follow-up visit. Joints were scanned for synovial hyperplasia, joint effusion and Power Doppler (PD) signal by two independent ultrasonographers. Patients were followed clinically for 3 years. A flare of synovitis was defined as a recurrence of clinically active arthritis. The association between clinical and MSUS variables with flare, was evaluated by adjusted logistic regression models. Results: 135 patients (78.5% F; median age 11.3 y; median disease duration 5.7 y; median CR duration 1.4 y) were included. Fifty-seven/135 (42.2%) patients had persistent oligoarthiritis; 41/135 (30.4%) extended oligoarthiritis; 32/135 (23.7%) polyarthiritis; 5/135 (3.7%) systemic arthritis. Seventy-eight/135 (57.7%) patients were in CR on medication. Subclinical synovitis was detected in 32/135 (23.7%) patients and in 53/7560 (0.7%) joints. Subclinical tenosynovitis was present in 20/135 (14.8%) patients. Subclinical synovitis was found more frequently in the ankle and wrist joints. 58.6% of patients showed persistent subclinical synovitis at 6 month follow up MSUS examination. During the 3-year follow up 45/135 (33.3%) patients experienced a disease flare (median survival time 2.2 y). PD positivity in tendons was the stronger independent risk factor of flare on multivariable regression analysis (HR: 4.8; P=0.04). Other predictors of flare were the JIA subtype (oligo-extended form: HR: 2.3; P=0.031) and the status of CR on medication (HR: 3.7; P=0.002). Conclusion: our results confirm that MSUS is more sensitive than clinical evaluation in the assessment of persistent synovial inflammation in JIA patients. Subclinical tenosynovitis was the best predictor of disease flare. To date, the role of tenosynovitis in the diagnosis and prognosis of JIA has been poorly investigated. Our results further support the role of MSUS, especially of the wrist and the ankle, in monitoring JIA patients in clinical remission and to predict disease flare. References: De Lucia O, et al. Baseline ultrasound examination as possible predictor of relapse in patients affected by juvenile idiopathic arthritis (JIA). Ann Rheum Dis. 2018 Oct;77(10):1426-1431. Filippou G, et al. The predictive role of ultrasound-detected tenosynovitis and joint synovitis for flare in patients with rheumatoid arthritis in stable remission. Results of an Italian multicentre study of the Italian Society for Rheumatology Group for Ultrasound: the STARTER study. Ann Rheum Dis 2018;77:1283-9.

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Soula, P. Ch Eugène. "Contribution à l'étude de la migraine." Paris : BIUM, 2004. http://www.bium.univ-paris5.fr/histmed/medica/cote?TPAR1884x035.

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ZANETTI, ANNA. "The management of patients with rheumatoid arthritis: an overview of obstacles and improvement strategies." Doctoral thesis, Università degli Studi di Milano-Bicocca, 2022. http://hdl.handle.net/10281/365542.

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L’artirite reumatoide (AR) è la più diffusa patologia autoimmune in Italia con elevati costi terapeutici e previdenziali associati. Questa patologia colpisce circa lo 0.5-1% della popolazione adulta, prevalentemente di genere femminile. Essendo una patologia degenerativa, i cui danni sono frequentemente irreversibili, una diagnosi precoce così come un adeguato trattamento ed un elevato livello di compliance del paziente allo stesso, potrebbero rallentare il peggioramento della malattia. Inoltre sono poco noti i possibili effetti della malattia e del suo trattamento sulle gravidanze e i successivi outcome gravidici. I principali obiettivi della tesi quindi sono: i) valutare l’aderenza alle linee guida per il trattamento dell’ AR da parte dei clinici, ii) valutare l’aderenza al trattamento per AR da parte del paziente, iii) stimare costo ed efficacia delle cure erogate nelle cliniche specializzate per il trattamento di pazienti con AR, iv) analizzare gli esiti gravidici e il raggiungimento della gravidanza in donne con AR trattate con metotrexate (MTX). La prima tematica ha riguardato la valutazione di come sono state implementate le linee guida della European Alliance of Associations for Rheumatology (EULAR) per il trattamento dell’AR e l’impatto dell’aderenza a queste linee guida sulla probabilità di ospedalizzazione. I principali risultati di questo studio hanno mostrato come i pazienti con un’ottima aderenza alle linee guida, se confrontati con quelli con bassa aderenza, abbiano un rischio del 24% inferiore di incorrere in ospedalizzazione. La seconda tematica ha riguardato la valutazione dell’impatto dell’aderenza al trattamento con Disease-Modifying Anti-Rheumatic Drugs (DMARDs), terapia suggerita dall’EULAR, sul raggiungimento della remissione clinica di malattia. I dati provengono dal database ELECTRA (con informazioni cliniche e provenienti da database amministrativi) di pazienti con AR trattati presso l’IRCCS Policlinico San Matteo (Pavia). Si è osservato che un incremento percentuale di 10 unità nella copertura al trattamento comporta un aumento della probabilità di remissione clinica del 10%. Da questi risultati sembra emergere l’importanza di riuscire a monitorare i pazienti nella pratica clinica per mantenere elevati standard di compliance. L’obiettivo della terza tematica si è focalizzato su una valutazione costo-efficacia del trattamento dei pazienti con AR erogato da cliniche specializzate (EAC), confrontandolo con quello dei pazienti trattati in cliniche non specializzate. Sono state quindi reclutate due coorti, la prima di pazienti trattati in una EAC e l’altra estratta dai database amministrativi di regione lombardia tra i soli soggetti con AR. I risultati principali di questa terza fase hanno mostrato come ad un incremento moderato dei costi si associ un incremento molto elevato dell’efficacia, specialmente se calcolata come durata di degenza e come aderenza alle linee guida EULAR. La quarta ed ultima tematica riguarda l’analisi dell’impatto del trattamento con MTX (DMARD suggerito dall’EULAR come prima linea di trattamento) nelle pazienti con AR sulla possibilità di raggiungere una gravidanza e sugli outcome gravidici conseguenti. Sono state definite tre coorti: donne con AR con esposizione incidente di MTX, donne con AR senza trattamento con MTX e donne senza AR. I risultati principali di questa analisi hanno mostrato che le donne con AR, specialmente se trattate con MTX, hanno una minor frequenza di gravidanze rispetto alle donne senza AR. Inoltre, le donne trattate con MTX sembrano avere un rischio più elevato di aborto spontaneo (circa due volte superiore) rispetto alle altre due coorti.
Rheumatoid arthritis (RA) is, in Italy, the most widespread autoimmune disease with high associated costs for the National Health Service. This disease affects about 0.5-1% of the adult population, mainly of the female gender. Being a degenerative disease, whose damages are frequently irreversible, an early diagnosis as well as an adequate treatment and a high level treatment compliance of the patient, could slow down the worsening of the disease. Furthermore, the possible effects of RA and its treatment on pregnancies and subsequent pregnancy outcomes are not well known. The main objectives of the thesis are therefore: i) to evaluate the adherence to guidelines for the treatment of RA, ii) to evaluate the patient's adherence to RA treatment, iii) to estimate the cost and effectiveness of care provided in specialized clinics for the treatment of RA patients, iv) to analyze pregnancy outcomes and the likelihood of achieving pregnancy in women with RA treated with methotrexate (MTX). The first issue concerned the assessment of how the guidelines of the European Alliance of Associations for Rheumatology (EULAR) for the treatment of RA have been implemented, and the impact of adherence to these guidelines on the probability of hospitalization. The main results of this study showed that patients with excellent adherence to guidelines, when compared with those with low adherence, have a 24% lower risk of hospitalization. The second topic concerned the evaluation of the impact of adherence to treatment with Disease-Modifying Anti-Rheumatic Drugs (DMARDs), the therapy suggested by EULAR, on the achievement of disease clinical remission (defined as a substantial decrease or absence of symptoms). The ELECTRA database, which contains clinical information and information from administrative databases of RA patients treated at the IRCCS Policlinico San Matteo (Pavia), was considered for the analysis. The main finding showed that a 10-unit percentage increase in proportion of days covered by DMARDs is associated with a 10% increase in the likelihood of clinical remission. These results show the importance of monitoring patients in clinical practice to maintain high levels of treatment compliance. The objective of the third theme focused on a cost-effectiveness evaluation, comparing RA patients treated in specialized clinics ("Early Arthritis Clinic" - EAC), with RA patients treated in non-specialized clinics. Two cohorts were recruited, the first one included patients treated in the EAC of the IRCCS Policlinico San Matteo and the other one with patients with RA extracted from the administrative databases of Lombardy region. The main results of this third phase showed that a moderate increase in costs is associated with a very high increase in effectiveness, especially if calculated as length of hospitalizations and as adherence to the EULAR guidelines. These findings could open up new scenarios in RA patient management. The fourth and final topic concerned the impact of treatment with MTX (DMARD suggested by EULAR as the first line of treatment) in RA women, on the likelihood of achieving pregnancy and on pregnancy outcomes. Three cohorts were recruited: women with RA with incident MTX exposure, women with RA without MTX treatment, and women without RA. The main results of this analysis showed that women with RA, especially when treated with MTX, have a lower frequency of pregnancies than women without RA. Furthermore, women treated with MTX have a higher risk of spontaneous abortion (about twice as high) than the other two cohorts.

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Cavaciocchi, F. "T CELL SUBTYPES IN MANAGEMENT OF OSTEOPOROSIS WITH BISPHOSPHONATES AND THE AUTOIMMUNE REACTION TO THE COLLAGEN IN RHEUMATOID ARTHRITIS." Doctoral thesis, Università degli Studi di Milano, 2015. http://hdl.handle.net/2434/251417.

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T lymphocytes with different T cell receptors are at the crossroad of inflammation and autoimmunity. We investigated the role of γδTCR and αβTCR T lymphocytes (γδT, αβT cells) in two model conditions represented by zoledronic acid (ZA)-induced acute phase reactions (APR) and in the immune reaction against collagen in rheumatoid arthritis (RA). First, γδTCR T lymphocytes (γδTcells) are specifically activated by ZA infusion in the treatment of osteoporosis and is frequently associated with the onset of APR, possibly via 25-OH vitamin D (25-OHvD) levels. 50% of patients reported ZA-associated APR (APR+). APR+ cases had a higher percentage of central memory Th1-like γδTcells before treatment. One week after ZA infusion, a decreased percentage of central memory Th1-like γδTcells, an increase in the percentage and activation of effector memory Th1-like γδTcells, and an increase in Th17-like γδTcells were observed in the patients with APR. Lower 25-OHvD levels were significantly associated to APR, but no correlation was found between 25-OHvD level and γδTcell percentage or subsets. Second, αβTCR T lymphocytes (αβTcells) in RA recognize the DR4/DR1-restricted epitope 261-273 of the human type II collagen, whereas B cells recognize the epitope 359-369. We investigated the role of B and T cell epitopes and their post-translational modifications on the RA adaptive immune response. PBMCs from 5 HLA-DR4+ monozygotic twins, two HLA-DR4+ and one HLA-DR3+ healthy donor and synovial fluids (SF) from an HLA-DR4+ RA patient and HLA-DR3+ patient were used and cells cultured with the native form of the collagen T epitope (261-273T), its K264 carbamylated form (homocit261-273T), the native form of the collagen B epitope (359-369B), its R360 citrullinated form (cit359-369B) or the combination of the native and modified epitopes. We may conclude that the collagen T epitope 261-273 has a role in the pathogenesis of RA, but the carbamilation of this epitope dos not seem to be influent in the T cell response.

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LO, MONACO Marika. "Relationship between clinical variables and Patient-Reported Outcomes in patients with psoriatic disease." Doctoral thesis, Università degli Studi di Palermo, 2021. http://hdl.handle.net/10447/499644.

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Background Psoriatic Arthritis (PsA) is a chronic inflammatory form of Arthritis associated with enthesitis, dactylitis, nail dystrophy, uveitis, and osteitis. PsA is strongly associated with comorbidities such as obesity, metabolic syndrome, and cardiovascular disease. As usual PsA patients are assessed either by rheumatologist or dermatologist but a multiprofessional assessment for those subjects is important to improve their disease control and their quality-of-life. The multidimensional assessment is a new model of care for PsA patients in which a multiprofessional team (rheumatologist, dermatologist, internal medicine physician, nutritionist and a phycologist) with a nurse as case manager, assess patients in the main domains of PsA from the admission to the follow-up. Different validated tools are used by the team to assess different patients’ dimension as patient-reported-outcomes. This study aimed to evaluate the association between and among clinical variables and Patient-Reported Outcomes in a realworld sample of PsA patients evaluated according the Multidimensional Assessment. Methods A cross-sectional study was conducted. Patients with PsA who signed the informed consent were enrolled at the PsA clinic at the ARNAS Civico in Palermo (Italy) from March 2018 to October 2020. Clinical, pharmacological, anthropometric, laboratory variables, and patientreported outcomes were evaluated, including: • Health Assessment Questionnaire (HAQ); • Facit-Fatigue (FACIT-F); • Psoriatic Arthritis Impact of Disease Questionnaire (PsAID); • Patient Health Questionnaire-9 (PHQ-9); • Disease Activity in PSoriatic Arthritis score (Dapsa); • Patient global assessment (PGA) STATA 14.1 was used to perform logistic analysis. Results According to CASPAR Criteria, 158 patients aged 55.2 (53.3 – 57.1) affected by Psoriatic Arthritis were included in the study. All the collected variables were evaluated ad a strong association was observed between functional disability measured by HAQ >2 and central obesity [OR (95% CI) 16.94 (2.22 - 129.48); p < 0.004]. Moreover, data analysis showed an association between high impact of disease on life (PsAID >4) and central obesity [OR (95% CI) 3.33 (1.56 - 7.13); p<0,002]. Models were adjusted for age, sex, years of illness, and biological treatment. Conclusion This study demonstrated a high association between functional disability studied subjectively using the HAQ, the impact of the disease on patients’ quality-of-life using the PsAID, and central obesity in patients affected by PsA. Data suggest that a multiprofessional evaluation for these patients is important to evaluate different aspect of the disease as the comorbidities. In particular, therapeutic goals should not be focused only on treatment but also on waist circumference reduction to reduce inflammation and improve patients’ functional ability and quality-of-life.

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Cassone, Giulia. "Caratteristiche cliniche e nuovi orizzonti diagnostico-terapeutici delle vasculiti dei grandi vasi e della interstiziopatia polmonare secondaria ad artrite reumatoide." Doctoral thesis, Università degli studi di Modena e Reggio Emilia, 2022. http://hdl.handle.net/11380/1288753.

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Le patologie reumatiche autoimmuni sono malattie croniche con un importante impatto sanitario in tutto il mondo. Il loro impatto economico e sociale deriva da una diminuzione della qualità della vita, dalla perdita di produttività e dall'aumento dei costi dell'assistenza sanitaria. Senza approcci adeguati alla gestione dei pazienti e al controllo di queste malattie, ci si può aspettare che questo impatto aumenti con il progressivo invecchiamento della popolazione. Attualmente, per alcune patologie reumatiche, mancano ancora accurati dati epidemiologici e rimane la necessità di progressi significativi in termini di diagnosi precoce, trattamento e gestione dei pazienti. Sezione A: L'arterite a cellule giganti (GCA) è la forma più comune di vasculite nei pazienti di età superiore ai 50 anni. Negli ultimi decenni molta attenzione è stata data al coinvolgimento extracranico dei grandi vasi, in particolare dopo lo sviluppo di nuovi strumenti di imaging come PET-TC, angio-RM (MRA) e angio-TC (CTA). Non è noto, tuttavia, quanto queste metodiche siano efficaci per valutare l'attività della malattia durante la terapia. Il trattamento della GCA si basa principalmente sull'uso a lungo termine di glucocorticosteroidi (GC). Tocilizumab è stato recentemente approvato per il trattamento della GCA, tuttavia viene spesso utilizzato in combinazione con GC, con conseguente alto rischio di effetti collaterali. Partendo da queste considerazioni, abbiamo realizzato uno studio osservazionale monocentrico per valutare le variazioni cliniche e di imaging in una serie di pazienti con GCA trattati con glucocorticosteroidi (GCs) per breve periodo e tocilizumab (TCZ) s.c. Abbiamo inoltre valutato l'efficacia e la sicurezza della monoterapia con TCZ come trattamento di mantenimento nella GCA. I nostri risultati preliminari hanno dimostrato che le tecniche di imaging sembrano essere utili nel valutare l'attività della malattia nei pazienti con GCA durante il trattamento. TCZ in monoterapia ha dimostrato un buon profilo di sicurezza nei pazienti con GCA, tuttavia il suo potenziale effetto nello stabilizzare o risolvere l'infiammazione dei grandi vasi senza l'uso concomitante di GC deve ancora essere dimostrato in ampi studi clinici randomizzati. Sezione B: L'artrite reumatoide (AR) è una malattia infiammatoria cronica che colpisce lo 0,5%-1% della popolazione mondiale. L’interstiziopatia polmonare (ILD) è la forma di coinvolgimento polmonare più comune dell'AR. Tutti gli studi disponibili sulla prevalenza di ILD in AR sono retrospettivi, con piccole serie di pazienti e numerosi bias, e quindi non affidabili. La diagnosi precoce rimane un essenziale ma difficile obiettivo clinico, in quanto l'aumento delle opportunità di diagnosticare l'ILD potrebbe migliorare la qualità della vita dei pazienti e diminuire la mortalità e l'elevato utilizzo delle risorse sanitarie. Sebbene il coinvolgimento polmonare rappresenti la seconda causa di morte nei pazienti con AR, non esistono approcci di screening randomizzati o linee guida di gestione di tale complicanza. Diversi agenti terapeutici sono stati suggeriti per il trattamento della RA-ILD, attualmente però non esistono studi clinici controllati randomizzati che supportino solide linee guida terapeutiche. In questo contesto, gli obiettivi di questo progetto di studio sono: -effettuare una revisione della letteratura e dello stato dell’arte sul trattamento dell'ILD nei pazienti con AR e discuterne i problemi irrisolti, anche suggerendo una proposta per la loro gestione clinica e analizzando l'evoluzione dell'RA-ILD nei pazienti trattati con tocilizumab e abatacept; -indagare l'utilità di uno strumento di screening tramite la rilevazione dei crepitii polonari a velcro e la loro analisi mediante un algoritmo opportunamente sviluppato; - eseguire uno studio osservazionale multicentrico prospettico internazionale per valutare l'incidenza e la prevalenza di ILD in pazienti con AR.
Autoimmune rheumatic diseases are chronic diseases with a major health impact worldwide. Their economic and social burden results from a decreased quality of life, lost productivity, and increased costs of health care. Without appropriate approaches to patient management and control of these diseases, this impact can be expected to increase as the population ages. Challenges in studying rheumatic diseases lie in achieving accurate epidemiological data and making efforts to obtain significant progress in terms of early diagnosis, treatment, and management of patients. Section A: Giant-cell arteritis (GCA) is the most common form of vasculitis in patients over 50 years old. Extra-cranic large vessel involvement (LVI) has emerged in recent decades, especially with the development of new imaging tools such as PET-TC, MR-Angiography (MRA) and CT-Angiography (CTA). It is unknown, however, how effective these methods are for assessing disease activity while patients are under treatment. GCA treatment is mainly based on long term use of corticosteroids (GCs). Tocilizumab has recently been approved for the treatment of GCA. However, it is often use in combination with GCs, with subsequent high risk of side effects. Starting from these considerations, we underwent a monocentric observational study to evaluate clinical and functional/morphological imaging variations in a series of patients with GCA treated with ultra-short corticosteroids (GCs) and tocilizumab (TCZ) s.c. We also evaluated effectiveness and safety of TCZ monotherapy as a maintenance treatment in GCA. In our preliminary results, radiologic tools seem to be useful methods for assessing disease activity in GCA patients during treatment. TCZ demonstrated a good safety profile in patients with GCA, however its potential effect in stabilize or resolve large vessels inflammation without the concomitant use of GCs has yet to be demonstrated in large randomized clinical trials. Section B: Rheumatoid arthritis (RA) is the most common chronic inflammatory disease, affecting 0.5%-1% of the population worldwide. Interstitial lung disease (ILD) is the most common and serious complication of lung involvement in RA. All the available studies about the prevalence of ILD in AR are retrospective, with small series of patients and numerous biases, and therefore not reliable. Moreover, this complication is often underrated, particularly in its earliest stages. An early diagnosis is challenging, and the increase of the opportunities to diagnose ILD could improve the quality of life of patients and decrease the mortality and the high utilization of healthcare resources. Although lung involvement represents the second cause of death in RA patients, there are no randomized screening approaches or management guidelines. Several therapeutic agents have been suggested for the treatment of RA-ILD, but nowadays there are no randomized controlled clinical trials to support therapeutic guidelines and treatment of RA-ILD is still based on empirical approaches. In this background, aims of this study project were: -to review the current literature on the treatment of ILD in RA patients and discuss the unsolved problems regarding this challenging patient cohort, even suggesting a framework for their management and analyzing the evolution of RA-ILD in patients treated with tocilizumab and abatacept; -to investigate the usefulness of detecting velcro crackle in lung sounds by analyze them using a suitably developed algorithm, as an early screening of RA-ILD; -to perform an international prospective multicenter observational study to evaluate incidence and prevalence of ILD in patients with RA.

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Guillot, Xavier. "Effets thérapeutiques et anti-inflammatoires de la cryothérapie dans les rhumatismes inflammatoires." Thesis, Besançon, 2016. http://www.theses.fr/2016BESA3009/document.

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La cryothérapie est utilisée de manière large et empirique à visée adjuvante dans les rhumatismes inflammatoires, avec un niveau de preuve faible. Dans une revue systématique de la littérature, en poolant les données de 6 études non contrôlées, nous avons pu démontrer que la cryothérapie (locale ou corps entier) appliquée deux fois par jour pendant 7 à 15 jours réduisait significativement l'EVA douleur et le score d'activité DAS25 dans la polyarthrite rhumatoïde. La cryothérapie locale (glace ou gaz froide) montrait par ailleurs des effets taille intra-classes supérieurs à ceux obtenus en utilisant la cryothérapie corps entier. L'objectif de ce travail était de mesurer les effets de la cryothérapie locale sur al douleur, l'inflammation synoviale et systémique chez les patients arthritiques et dans le modèle murin d'arthrite à l'adjuvant. Dans les études randomisées CDRI et ALGGAR, nous avons évalué les effets de deux applications locales de froid (glace versus gaz froid) sur la douleur, l'activité Doppler et les taux protéiques de cytokines intra-articulaires controlatéraux non souffrant d'arthrites de genou non septiques. Les genoux arthritiques controlatéraux non traités étaient utilisés comme contrôles. Nous avons par ailleurs étudié in vitro les effets de l'hypothermie modérée (30°C pendant 2heures) sur l'expression protéique des cytokines dans un modèle de culture de rotules de rats arthritiques. Nous avons enfin étudié in vitro dans l'arthrite à l'adjuvant les effets de l'application sub-chronique de glace ou de gaz froid (2 fois par jour pendant 14 jours versus contrôles arthritiques non traités) sur le score d'arthrite, le diamètre de cheville, la transcription des gènes codant pour les cytokines pro-inflammatoires dans les pattes arrières (Q-RT-PCR) et l'expression protéique des cytokines dans le plasma (Multiplex et ELISA) après 14 jours de traitement. Dans l'étude CDRI, la cryothérapie locale (glace et gaz froid) réduisait significativement l'EVA douleur ainsi que le score Doppler dans les genoux traités, ces effets persistant le lendemain des deux applications. Dans une analyse intermédiaire des résultats de l'étude ALGGAR, en combinant les deux groupes de traitement (glace et gaz de froid), nous avons observé une baisse des taux d'IL-6, d'IL-1β et de VEGF dans le liquide articulaire arès deux applications. dans les cultures d'explants de rotules de rats arthritiques, l'hypothermie ponctuelle réduisait significativement les taux d'IL-6, IL-17A et IL-1β dans les pattes arrières après 14 jours de traitement. Les deux modalités réduisaient significativement les niveaux plasmatiques d'IL-17A et la glace réduisait en outre les taux d'IL-6 et de VEGF. Nous n'avons observé aucun effet de la cryothérapie locale sur le voie du TNF-α chez l'homme ni chez l'animal. Nos résultats démontrent pour la première fois un effet thérapeutique et anti-inflammatoire de la cryothérapie locale dans l'arthrite. Les effets biologiques était IL-6/IL-147 dépendants et TNF-α indépendants. Des études complémentaires permettront de mieux caractériser les mécanismes moléculaires sous-jacents et de déterminer su la cryothérapie locale pourrait être une alternative aux AINS et corticoïdes dans les rhumatismes inflammatoires
Cryotheapy i widely and empirically used in an adjuvant setting in inflammatory rheumatic diseases, with a low level of evidence. We performed a systematic review of the literature and, by pooling data from 6 non-controlled studies, we could show that local cryotherapy (local or whole-body cryotherapy) applaied twice a day for 7-15 days significantly reduced the pain VAS and the DAS28 activity score in rheumatoid arthritis. Furthermore, local cryotherapy (ice packs or cold gas) showed significantly greater intra)class effect-sizes compared to whole-body cryotherapy. The aim of this work was to measure the effects of local cryotherapy on pain, synovial and systemic inflammation in arthrici patients and in the murine model of adjuvant-induced arthritis. First, in the CDRI and ALGGAR randomized studies, we evaluated the effects of 2 local cold applications (ice versus cold gas) on pain, power Doppler activity and intra-joint cytokine protein levels in 46 patients suffering from non-septic knee arthritides. Contralateral arthritic knee were used as control. Secondly, we studied the in vitro effects of mild hypothermia (30°C for 2 hours) on cytokine protein expression in a model of cultured arthritic rat patellae. Thidly, we studied the in vitro effects of sub-chronically applied ice or cold gas (twice a day for 14 days versus non-treated arthritic controls) on the arthritis score, the ankle diameter, pro-inflammatory cytokine gene transcription levelsin hind paws (Q-RT-PCR) and cytokine plasma protein levelx (Multiplex and ELISA) after 14 days of treatment. In the CDRI study, local cryotherapy (ice and cold gas) significantly reduced the pain VAS and the power Doppler score in treated kness, and these effects remained significant the day afetr 2 cold applicaitions. In an intermediate analysis of the ALGGAR study results, by pooling the 2 treatment groups, we could show significant decreases in IL-6 protein, IL-1β and VEGF synovial fluid protein levels after 2 cold applicatios. In arthritic rat patella explangt culture experiments, punctual hypothermia significantly reduced IL-6 protein levels. In vivon ice was more efficient on the clinical parameters and better tolerated compared to cold gas. Both techniques significantly reduced IL-6, IL-17A ans IL-1β gene transcription levels in hind paws after 14 days of treatment. Both techniques redcued IL-17A plasma protein levles, while ice also reduced IL-6 and VEGF plasma protein levels. Conversely, we observed no effect of local cryotherapy on the TNF-α pathway, neither in patients nor in our animal model. Here we demonstrate for the first time therapeutic and anti-inflammatory effet-cts of local cryothepary in arthritis. The biological effects were IL-6/IL-17-driven and TNF-α independent. Further studies will help elucidate the underlying molecular mlechanisms involved and detemrine whether local cryotherapy might be a safer alternative to NSAIDs ans corticosteroids in inflammatory rheumatic diseases

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Sukubo, N. G. "NO CODING RNAs IN MACROPHAGE POLARIZATION: THE RELEVANCE OF THE "JUNK" RNA." Doctoral thesis, Università degli Studi di Milano, 2016. http://hdl.handle.net/2434/365870.

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Abstract Form the central dogma of the biology formulated by Crick in 1958, to the detection of “junk RNA”, a new prospective has been open. Macrophages are essential cell of the innate immunity system important in onset and resolve inflammation. Moreover they are important in the cross-talk with adaptive immunology. It is also clear that macrophages are involved in many chronic diseases such as atherosclerosis, asthma, rheumatoid arthritis. In these pathologies there is an anomalous prolongation/amplification of the macrophage challenge to lead homeostasis. In this landscape favor macrophage activation and re-programming. Mantovani and colleagues have schematically categorized macrophages in “classical” (M1) activated, triggered with microbial stimuli (e.g. LPS) alone or together with the TLR eliciting; and “alternative” (M2) cell types, activated by IL-4/IL-13. The identification of the underlying molecular mechanisms on the base of this process may suggest new approaches to interfere with chronic inflammation and other inflammatory disease, such as cancer. The aim of this presented work was to characterize the epigenetic mechanism involved in macrophage polarization. To better elucidate this purpose the thesis was divided in three macro chapter: • MicroRNA-135b: the pivot of the macrophage polarization balance; • The “junk” RNA controlled by glucocorticoids: miR-135b and its host gene BLACAT1; • MicroRNA-135b in gouty arthritis. Overall, we identified a specific miRNome in human classic and alternative polarized macrophages (69 differential expressed miRNAs among the subsets). In addition, we pointed out the impact of miR-135b a de novo expressed miRNA in M1 macrophages, and for the first time associated with macrophages in an inflammatory diseases such as gouty arthritis. Indeed we demonstrated that miR-135b locus is activated by the inflammatory stimulus, LPS, which discharge the repressor complex polycomb2. Although, we can classified miR-135 as M1-associated or induced, which damps M2 phenotype in favor of the M1 thru the targeting of important the transcription factor, c-MYC, STAT6 and KLF4, sustaining the inflammation. In addition miR-135b expression is inhibited by the anti-inflammatory cytokine IL-10, to highlight its pro-inflammatory role; the same results was assess for miR-155. We have shown in the model of gouty arthritis, miR-135b is induced during the progression of the inflammation by macrophages. However it provides a negative feedback to limit excessive macrophage response to MSU crystal, thru the targeting of the IL-1β pathway. These results confirm the relevance of miR-135b as an important hinge of macrophage polarity. At the light of these observations, the identification of the underlying process that regulates the expression of miR-135b will be essential. miR-135b is located in the intron of the lncRNA, BLACAT1. We glimpsed that the induction of miR-135b and BLACAT1 is not correlated; on the contrary BLACAT1 is induced by anti-inflammatory stimulation, influencing miR-135b. Although we can speculate a novel type of regulation beyond IL-10, used by the macrophages to control the expression of this miRNA. Probably with the action of the MCP-induced protein 1 (MCPIP1), which is induced downstream LPS and IL-1β pathway and has been shown to suppress miR-135b biosynthesis in cancer.

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Martire, Delphine. "Potentiel thérapeutique des lymphocytes régulateurs de type 1 (Tr1) dans l'arthrite expérimentale." Thesis, Montpellier 1, 2013. http://www.theses.fr/2013MON1T025.

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Objectifs : Les lymphocytes T régulateurs de par leur rôle primordial dans l'homéostasie de la réponse immune sont des cellules idéales pour une immunothérapie antigène-spécifique dans les maladies auto-immunes. Les lymphocytes T régulateurs de type 1 ou Tr1 sont caractérisées par une forte sécrétion d'IL-10, cytokine qui joue un rôle déterminant dans leur capacité à supprimer des réponses immunes pathologiques dans différents contextes. L'objectif de ma thèse est d'évaluer le potentiel thérapeutique de cellules Tr1 spécifiques du collagène de type II (col-Treg) dans deux modèles de polyarthrite rhumatoïde (PR) chez la souris. Méthode : Les clones Col-Treg ne possèdent pas de marqueurs membranaires spécifiques mais sont caractérisés par un profil cytokinique particulier (IL10highIL4negIFN-γint) et par leur capacité de suppression in vitro. Tout comme les Tregs naturels, ils expriment une quantité importante de GITR, de CD39 et de Granzyme B. Une simple injection de cellules Col-Treg réduit l'incidence et les symptômes cliniques de l'arthrite à la fois de manière préventive et curative, avec un impact significatif sur les anticorps anti-collagène de type II. En outre, l'injection de Tr1 antigène spécifique in vivo diminue de manière significative la prolifération des cellules T antigène spécifique. Conclusion : Nos résultats démontrent le potentiel thérapeutique des cellules Col-Treg dans deux modèles d'arthrite expérimentale prouvant que les cellules Col-Treg représente une nouvelle approche thérapeutique de choix pour le traitement des patients atteint de polyarthrite et réfractaires aux traitements actuels
Objectives : Regulatory T (Treg) cells play a crucial role in preventing autoimmune diseases and are an ideal target for therapies to suppress inflammation in an antigen-specific manner. Type 1 Treg cells (Tr1) are defined by their capacity to produce high levels of IL10, which contributes to their ability to suppress pathological immune responses in several settings. The aim of my PhD was to evaluate the therapeutic potential of collagen type II-specific Tr1 (Col-Treg) cells in two models of rheumatoid arthritis (RA) in mice. Methods : Col-Treg clones were isolated and expanded from Collagen-specific TCR transgenic mice. Their cytokine secretion profile and phenotype characterization were studied. The therapeutic potential of Col-Treg cells was evaluated after adoptive transfer in collagen-antibodies- and collagen-induced arthritis models. The in vivo suppressive mechanism on effector T cell proliferation was also investigated. Results : Col-Treg clones are characterized by a cytokine profile (IL10highIL4negIFN-γint) and mediate contact-independent immune suppression. They also share with natural Tregs high expression of GITR, CD39 and Granzyme B. Single infusion of Col-Treg cells reduced incidence and clinical symptoms of arthritis both in preventive and curative settings, with a significant impact on collagen type II antibodies. Importantly, injection of antigen-specific type 1 Treg cells decreases significantly the proliferation of antigen-specific effector T cells in vivo. Conclusion : Our results demonstrate the therapeutic potential of Col-Treg cells in two models of RA, providing evidence that Col-Treg could be an efficient cell-based therapy for RA patients refractory to current treatments

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Lozano, Claire. "Rôle de mir-342-3p dans l'hétérogénéité fonctionnelle des ostéoclastes et implication dans l’arthrite auto-immune." Thesis, Montpellier, 2020. http://www.theses.fr/2020MONTT016.

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Les micro-ARNs (miARNs) sont de petits ARN simples brins non codants qui contrôlent l’expression des gènes au niveau post-transcriptionnel, dans de nombreux processus cellulaires. Ils jouent un rôle clé dans la régulation de l’ostéoclastogenèse, un processus de différenciation cellulaire qui aboutit à la formation d’ostéoclastes (OCs). Les OCs sont des cellules multinucléées du tissu osseux issus de précurseurs myéloïdes. Ce sont les seules cellules de l’organisme capables de résorption osseuse, donc essentielles à l'homéostasie osseuse et au renouvellement osseux. Toute anomalie de leur fonctionnement est associée à des pathologies osseuses. Dans le cas de la polyarthrite rhumatoïde (PR), les OCs participent activement à l'érosion osseuse. La PR est une maladie auto-immune invalidante caractérisée par une atteinte articulaire inflammatoire associée à une destruction du cartilage et de l’os. Il a été décrit différents types d’OCs sur la base de leurs propriétés immunologiques : les OC tolérogènes (t-OCs) et les OC inflammatoires (i-OCs). Des études récentes ont montré que les i-OCs dérivent exclusivement de précurseurs circulants qui infiltrent les articulations arthritiques. Mon travail a consisté à combiner les analyses du miRNome et du transcriptome des sous-types t-OCs et i-OCs, en contexte physiologique et arthritique, afin d’identifier des miARNs spécifiques de chaque type d’OCs et les voies biologiques associées. Parmi les miARNs associés aux i-OCs, j’ai identifié miR-342-3p, encore non décrit dans l’ostéoclastogenèse ou l’arthrite. J’ai montré que miR-342-3p a un effet pro-ostéoclastique in vitro en soutenant la phase précoce de l’ostéoclastogenèse par induction de la survie et de la motilité des précurseurs myéloïdes. J’ai optimisé l’inhibition de miR-342-3p dans les précurseurs des i-OCs dans le modèle murin de l’arthrite auto-immune (K/BxN serum-transfer arthritis, STA) par l’administration systémique ou locale d’un inhibiteur ou agoniste de miR-342-3p formulé avec le liposome cationique DMAPAP/DOPE. J’ai montré le ciblage des monocytes inflammatoires Ly6Chigh du sang et de l’articulation, associée à l’inhibition d’Adam17 quand un lipoplex miR-342-3p est injecté. J’ai enfin montré qu’Adam17 est une nouvelle cible de miR-342-3p dans les précurseurs OCs. Mes travaux suggèrent que la modulation in vivo de l’expression de miR-342-3p dans les précurseurs des i-OCs pourrait être une stratégie thérapeutique intéressante pour réduire l’érosion osseuse liée à l’arthrite
MicroRNAs (miRNAs) are small, single-strand non-coding RNAs that negatively regulate gene expression at the post-transcriptional level in many cellular processes. They play a key role in the regulation of osteoclastogenesis, a process of cell differentiation that leads to the formation of osteoclasts (OCs). OCs are multinucleated cells located in bone tissue that derived from myeloid precursors. OCs are the only cells capable of bone resorption, which role is essential to bone homeostasis and turnover. However, they actively participate in bone erosion in rheumatoid arthritis (RA), an autoimmune disease characterized by chronic joint inflammation associated with destruction of cartilage and bone. Based on their immunological properties, two OC subsets have been identified, the so called tolerogenic OCs (t-OCs) and inflammatory OCs (i-OCs). Recent studies have shown that the i-OCs associated with arthritis exclusively derive from circulating Ly6Chigh precursors that infiltrate inflamed joints. Combining miRNome and RNA-Seq analyses of t-OC and i-OC subsets, I aimed at identifying miRNAs markers specific for each subset and associated biological pathways. Among the miRNAs associated with i-OCs, I identified miR-342-3p, neither described yet in osteoclastogenesis or in arthritis. I demonstrated that miR-342-3p has a pro-osteoclastic effect in vitro by supporting the early phase of osteoclastogenesis, through the control of survival and motility of the precursors. I optimized the delivery of miR-342-3p agonist or neutralizing molecules in the precursors of i-OCs using the mouse model of autoimmune arthritis (K/BxN serum-transfer arthritis, STA) and the cationic liposome DMAPAP/DOPE. I showed that the systemic or intra-articular administration of miR-342-3p lipoplex selectively targets blood and joint inflammatory Ly6Chigh monocytes, and that in vivo neutralization of miR-342-3p in Ly6Chigh OC precursors of STA mice increased Adam17 expression. I identified Adam17 as a novel target for miR-342-3p. Overall, my data indicate that the in vivo modulation of miR-342-3p expression in i-OC precursors could be a potential therapeutic strategy to reduce bone erosion in arthritis

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Presumey, Jessy. "Cibler les monocytes inflammatoires par ARNi pour une immunothérapie innovante des maladies autoimmunes." Thesis, Montpellier 1, 2011. http://www.theses.fr/2011MON1T017/document.

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Les monocytes inflammatoires Ly-6Chigh murins, et leurs homologues humains CD14+CD16-, jouent un rôle important dans l'initiation et la persistance des maladies inflammatoires chroniques. Leur action délétère dans ces pathologies a mené au développement de stratégies thérapeutiques visant à les éliminer ou empêcher leur recrutement aux sites inflammatoires. Toutefois, ces méthodes se sont avérées peu spécifiques des monocytes et surtout d'une faible efficacité compte tenu de l'aspect hautement inflammatoire des monocytes. Le besoin de développer de nouvelles stratégies est donc nécessaire. Les objectifs de ma thèse ont donc été dans un premier temps de caractériser in vivo le ciblage spécifique des monocytes inflammatoires par la formulation liposomale DMAPAP. Dans un second temps, l'utilisation de DMAPAP pour formuler des siRNA a permis d'évaluer l'efficacité thérapeutique d'une stratégie basée sur l'inhibition spécifique de gènes jouant un rôle clef dans l'inflammation dans les monocytes inflammatoires. Mon travail a permis de montrer dans un modèle préclinique d'arthrite que l'inhibition de gènes régulateurs de l'inflammation dans les monocytes Ly-6Chigh est une approche thérapeutique efficace permettant d'induire une immunomodulation des réponses pathogéniques des lymphocytes T effecteurs, aboutissant au défaut de recrutement des cellules immunitaires dans les articulations et à une amélioration des signes cliniques. J'ai également validé le transfert de cette technologie ex vivo sur cellules humaines primaires. L'inhibition de gènes clefs dans les monocytes inflammatoires représente donc une stratégie prometteuse pour le développement de futures thérapies dans la polyarthrite rhumatoïde. Par ailleurs, mes résultats confirment le rôle central des monocytes inflammatoires dans les pathologies inflammatoires chroniques
Inflammatory mouse Ly6Chigh monocyte subset and its human counterpart, defined as CD14+ CD16-, play key roles in the initiation and chronicization of immune-mediated inflammatory disorders (IMID). Deleterious effects of monocytes led to the development of therapeutic strategies aiming at depleting them or preventing their recruitment to inflamed tissues. However, these methods are poorly specific with weak efficacy considering the high number of inflammatory monocytes and their marked level of activation. The need for developing new therapeutic approaches is obvious. The aim of my thesis was to characterize selective delivery of a siRNA-containing lipid formulation to the Ly-6Chigh monocyte population and at evaluating the therapeutic potential of this targeted strategy. Using the cationic lipid-based DMAPAP vehicle for in vivo RNAi-mediated gene silencing, my work allowed demonstrating, in a preclinical mouse model of arthritis, the efficacy to inhibit master genes of inflammation specifically within Ly-6Chigh monocytes upon systemic injection. Reduced disease severity in mice was associated with an overall systemic immunomodulation of the pathogenic T cell populations and led to defective mobilization of immune cells to arthritic joints. Importantly, the formulation was successfully optimized in a perspective of clinical application and the targeting of human CD14+CD16- inflammatory monocytes was validated ex vivo. Overall, my findings demonstrate that the silencing of a key gene within Ly-6Chigh monocytes is a promising strategy for future therapeutic intervention in the context of IMID and reinforces the pivotal role of Ly-6Chigh monocytes in inflammatory processes

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Vugler, Alexander David. "Predicting anti-arthritic drug effects in collagen-induced arthritis using short-term mechanistic models of collagen II immunity." Thesis, Open University, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.494617.

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Novel anti-arthritic drugs are often assessed in murine collagen-induced arthritis (CIA), which is a widely used pre-clinical model of rheumatoid arthritis. However, CIA studies are lengthy, development of arthritis is not synchronised and not all animals develop disease. Work conducted in this thesis addressed some of these issues by developing short-term mechanistic models of collagen II (CII) immunity. Drug effects on Cll-induced hypersensitivity, anti-CII antibodies and ex vivo CII stimulated CD4⁺ T cell proliferation in mice 14 days post-CII sensitisation were assessed and compared to their anti-arthritic effect in CIA.

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Paquet, Joseph. "Potentialités anti-inflammatoires de l'inhibition génomique et transcriptionnelle du TNF-[alpha] par une approche de type oligonucléotidique." Thesis, Nancy 1, 2010. http://www.theses.fr/2010NAN10067/document.

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Le Tumor Necrosis Factor alpha (TNF-[alpha]) est une cytokine pro-inflammatoire qui occupe un rôle central dans la physiopathologie de nombreuses pathologies inflammatoires et particulièrement l'arthrite. La neutralisation de cette cytokine par l'utilisation d'anticorps anti-TNF-[alpha] a montré son efficacité dans la polyarthrite rhumatoïde et est aujourd'hui le traitement de référence pour la prise en charge de cette pathologie. Cependant, un tiers des patients traités par anticorps anti-TNF restent réfractaires ou ne répondent pas à ce traitement. Dans ce contexte, il apparait nécessaire de développer des approches nouvelles ou complémentaires pour renforcer l'arsenal thérapeutique actuellement disponible. L'utilisation d'oligonucléotides triple hélice (TFO) permet de moduler l'expression génique de manière spécifique par interaction avec la double hélice d'ADN. Dans cette étude, nous avons évalué les potentialités anti-inflammatoires d'un TFO anti-TNF-[alpha] in vitro sur les synoviocytes et chondrocytes articulaires et in vivo dans deux modèles d'arthrite expérimentale. Ce TFO interagit avec le promoteur du gène du TNF-[alpha], et son activité inhibitrice a été comparée à celle d'une approche par ARN interférence in vitro. Dans les modèles d'arthrite aigue et chronique, l'injection intra-articulaire préventive de TFO anti-TNF-[alpha] permet une amélioration significative des symptômes arthritiques. Particulièrement, le traitement par le TFO diminue sensiblement l'inflammation synoviale et les lésions ostéocartilagineuses articulaires. Ces résultats sont les premiers à montrer la possibilité d'utiliser un TFO in vivo et offrent d'intéressantes perspectives thérapeutiques
Tumor necrosis factor alpha (TNF-[alpha]), a pro-inflammatory cytokine, plays a key role in the pathogenesis of many inflammatory diseases, including arthritis. Neutralization of this cytokine by anti-TNF-[alpha] antibodies has shown its efficacy in rheumatoid arthritis and is now widely used. Nevertheless, some patients currently treated with anti-TNF-[alpha] remain refractory or become non-responder to these treatments. In this context, there is a need for new or complementary therapeutic strategies. Triplex forming oligonucleotides (TFO) can inhibit gene expression with high sequence-specificity by interacting with the DNA double-strand. In this study, we investigated if an anti-TNF-[alpha] TFO had a therapeutic activity on inflammatory processes in vitro and in vivo, as judged from effects on two rat arthritis models. This TFO interacted with the TNF-[alpha] gene promoter, and its inhibitory activity was verified and compared to that of siRNA in vitro. A local intra-articular preventive injection of TFO in both acute and chronic arthritis models significantly reduced the development of the disease. Furthermore, the TFO efficiently blocked synovitis and cartilage and bone destruction in the joints. The results presented here provide the first evidence that gene targeting by anti-TNF-[alpha] TFO modulates arthritis in vivo, thus providing proof of concept that it could be used as therapeutic tool for TNF-[alpha]-dependent chronic inflammatory disorders

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Hablot, Julie. "Liens entre inflammations articulaire et digestive : étude expérimentale chez la souris et contribution de l’immunité mucosale." Thesis, Université de Lorraine, 2018. http://www.theses.fr/2018LORR0095/document.

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Des cellules immunitaires appartenant à l’immunité de type 3 sont localisées dans muqueuse digestive. Les micro-organismes du microbiote stimulent le système immunitaire pour le maintenir en veille face à de potentiels agents infectieux, tout en ayant une tolérance pour les micro-organismes commensaux. Des études montrent des anomalies du microbiote intestinal chez les patients arthritiques. Ceci suggère une dérégulation de l’immunité mucosale digestive dans la survenue de l’inflammation articulaire. Des cellules de l’immunité mucosale pourraient migrer vers les sites articulaires, notamment grâce à des récepteurs aux chimiokines. Le facteur RORγt, indispensable à la différenciation des cellules de l’immunité de type 3, est régulé négativement par le récepteur PPARγ. A l’aide de modèle murins, nous avons étudié l’impact de l’invalidation de PPARγ et de l’inhibition du récepteur aux chimiokines CCR3 sur les relations entre sphères digestive et articulaire. Nous avons montré que l’induction d’une colite au cours d’une arthrite au collagène modifie le microbiote intestinal, retarde l’apparition et diminue la sévérité des lésions articulaires. Nous avons démontré que les souris PPARγ-/- développent spontanément une inflammation articulaire associées à des anomalies dans la répartition des cellules immunitaires de type 3 de la muqueuse digestive. Ces souris sont dysbiotiques avec une flore enrichie notamment en entérobactéries, mais non-arthritogène. Enfin, l’inhibition de CCR3 au cours du développement d’une arthrite au collagène retarde et diminue la sévérité de la pathologie et altère la répartition des leucocytes dans les articulations et de la muqueuse digestive
Numerous type 3 immune cells (Th17 and ILC3) are physiologically located in lamina propria of the intestine. Microbial agents within the gut shape the immune system to make it efficient against threats but peaceful with commensals. Recent studies demonstrated changes in gut microbiota composition (dysbiosis) in chronic inflammatory rheumatism. These results suggest a role for mucosal immunity alteration in articular inflammation occurrence. Indeed, some type 3 immune cells once activated by microbiota, are thought to migrate to joints, involving notably chemokines receptors. Transcription factor RORγt, the master regulator of type 3 immune cells, could be negatively regulated by nuclear receptor PPARγ. Using experimental murine models, we studied the consequence of PPARγ deficiency and consequence of the chemokine receptor CCR3 inhibition on the joint-gut axis. Firstly, we demonstrated that experimental colitis induces microbiota changes, delays and reduces collagen-induced arthritis severity. Secondly, we showed that PPARγ deficient mice display spontaneous joint inflammation associated with abnormal type 3 distribution within the gut. Dysbiosis with enrichment in facultative anaerobic Enterobacteriaceae was found in these mice. Fecal microbiota transfer demonstrated this microbiota is non-arthritogenic. Finally, we demonstrated that CCR3 inhibition has profound anti-arthritic potencies associated with changes in leukocytes distribution within the joint-gut axis

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Quentin, Julie. "Immunomodulation de l'arthrite expérimentale par les cellules dendritiques tolérogènes." Thesis, Montpellier 1, 2011. http://www.theses.fr/2011MON1T018/document.

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Immunomodulation de l'arthrite expérimentale par les cellules dendritiques tolérogènes. Les cellules dendritiques (DCs) sont des cellules présentatrices d'antigènes jouant un rôle clé dans l'initiation et la modulation des réponses immunitaires. En effet, en parallèle de leur capacité à initier une réponse immunitaire adaptative, les DC sont également impliquées dans les mécanismes de tolérance périphérique. Elles sont utilisées depuis 10 ans maintenant en clinique dans des stratégies thérapeutiques anti-tumorale et leurs propriétés tolérogènes ouvrent aujourd'hui leur champ d'applications à des pathologies autoimmunes, l'asthme et la transplantation afin de restaurer une homéostasie de la réponse immune. Les objectifs de ma thèse ont consisté à :- renforcer le potentiel tolérogène des DCs par manipulation in vitro- tester la capacité de DCs tolérogènes à induire une protection de l'arthrite expérimentale- identifier les mécanismes cellulaires et moléculaires impliqués dans la tolérance induite par les DCs. Mon travail de thèse a permis de montrer l'efficacité de la vaccination de souris arthritiques avec des DCs immatures conservant leurs propriétés tolérogènes in vitro et in vivo, grâce au traitement préalable avec un agent immunosuppresseur, la rapamycine. L'injection répétée de DCs immatures induit la génération de lymphocytes T régulateurs CD4+ CD49b+ sécrétant de l'IL-10 ayant de fortes capacités immunosuppressives. Ce projet a permis de mettre en évidence l'efficacité des DCs dans le traitement d'une pathologie autoimmune déjà établie et l'implication d'une population cellulaire régulatrice originale
Tolerogenic dendritic cells for immumodulation in experimental arthritis.Dendritic cells (DCs) are the most potent antigen-presenting cells that play critical roles in the initiation and regulation of immune responses. Based on their tolerogenic properties, DCs offer potential as therapeutic tools to ameliorate or prevent graft rejection or graft-versus-host disease, or to treat autoimmune disorders.The objectives of my PhD consisted to:- reinforce the tolerogenic potential of DCs by in vitro handling.- assess the capacity of such tolerogenic DCs to induce a protective response in experimental autoimmune arthritis- identify cellular and molecular mechanisms implied in the tolerogenic DCs-induced protectionOur results suggest that, in contrast with conventional DCs, the rapamycin-conditioned iDCs maintain their tolerogenic potential upon injection in inflammatory settings and are able to dampen an already Th1-primed immune response, conferring a protection from arthritis. The protection of the mice was associated with an expansion of the IL-10-secreting CD49b+ Treg in the spleen and liver of the injected mice and a decrease of the Th1 immune response. These results underscore the therapeutic potential of tolerogenic DCs in an established autoimmune disease as well as the anti-inflammatory potential of the CD49b+ Treg cell population induced following DC vaccination

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Spilis, Angelica Abby. "Dancing With Arthritis." Master's thesis, Temple University Libraries, 2015. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/327134.

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Dance
M.A.
This Master of Arts thesis is based on research that I conducted on dancers who have the auto-immune disease of Rheumatoid Arthritis. Rheumatoid Arthritis is a long-term autoimmune disease that causes inflammation in the joints and the surrounding tissues. Dancers with arthritis feel pain the joints that can be minor or severe, depending on how they are moving their bodies. This research investigates how dancers with an arthritic body can dance without the experiencing pain in their joints. Arthritis impairs movement because it is a disease that affects the joints. In this thesis, I created movements that could enable arthritic dancers the opportunity to continue dancing. I have identified a movement vocabulary, movement methods, and strategies for arthritic dancers who want and need to move with minimal pain. Movements have been created specifically for the arthritic body. I use my own experiences and challenges as an arthritic dancer to inform this study. My experiences helped me to create movements specifically for arthritic dancers because I am an advocate for those who suffer from arthritis.
Temple University--Theses

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Hermann, Kay-Geert. "Die rheumatoide Arthritis." Doctoral thesis, Humboldt-Universität zu Berlin, Medizinische Fakultät - Universitätsklinikum Charité, 2000. http://dx.doi.org/10.18452/14542.

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Multimedia - Wort des Jahres 1995 - taucht als populärer Begriff in allen Bereichen unserer Gesellschaft auf. Auch an Universitäten erhofft man sich durch die Einführung von computerunterstützten Lernformen eine höhere Qualität der Lehre sowie Kosteneinsparungen. Nach ersten Versuchen in den 60er Jahren war das Neue in den 90ern die realitätsnahe, multimediale Simulation von Entscheidungssituationen. Auf dem Gebiet der Rheumatologie ist derzeit jedoch noch ein Mangel an deutschsprachigen Softwaretiteln zu erkennen. Ziel war die Erstellung eines multimedialen Kompendiums über die rheumatoide Arthritis für den Einsatz in der universitären und postgraduierten Lehre. Das System soll als elektronisches Nachschlagewerk und als Basis für interaktive Diashows geeignet sein. Mit Hilfe eines Apple Macintosh und der Autorensoftware Macromedia Director wurde eine CD-ROM entwickelt, die sowohl für Macintosh- als auch für Windows-Computer geeignet ist. Die Beschreibung der Symptome der rheumatoiden Arthritis und der erforderlichen Untersuchungstechniken nimmt mit 31% der Bildschirmseiten den größten Teil des vorliegenden Multimedia-Kompendiums ein. Weitere Schwerpunkte wurden auf Pathogenese (19%), bildgebende Verfahren (14%), Differentialdiagnosen (11%), Therapie (10%) und Laboruntersuchungen (7%) gelegt. Videos und Animationen dienen der Illustration zellulärer Vorgänge und der Zusammenfassung klinischer Untersuchungstechniken. Etablierte Kriterienkataloge für elektronische Medien dienten der Qualitätssicherung im Entwicklungsprozeß. Eine parallel durchgeführte formative Evaluation lieferte erste Erkenntnisse über Praxistauglichkeit und Stabilität des Programmes, ohne jedoch eine fundierte summative Evaluation ersetzen zu können. Multimedia-Lehrbücher wie das vorliegende Kompendium stellen für den konventionellen Unterricht eine ideale Ergänzung zum klassischen Lehrbuch dar und dienen für die problemorientierte Ausbildung als schnell zur Verfügung stehende Wissensbasis. Jedoch blieben bei der fakultativen Nutzung von computerbasierten Lernmöglichkeiten in Lernzentren die Ergebnisse bisher hinter den Erwartungen zurück. Es ist zu diskutieren, inwieweit die Vorteile der Multimedia-Technologie durch gezielte Integration in das Curriculum an deutschen Hochschulen zu Kosten- und Zeitersparnissen führen können.
Multimedia - word of the year 1995 in Germany - is a popular term cropping up in all areas of society. Universities, too, hope to improve the quality of teaching and to cut costs by introducing computer-based forms of learning. Following initial attempts in the sixties, a new aspect introduced in the nineties was the life-like multimedia simulation of decision-making situations. In medicine, there still is a lack of German-language software packages in rheumatology. The aim of the present project was to develop a multimedia compendium on rheumatoid arthritis for teaching at the university and postgraduate level. The system was intended to serve both as an electronic work of reference and as a basis for interactive slide presentations. Using the authoring tool Macromedia Director on an Apple Macintosh computer, a CD-ROM was developed that can be run on Macintosh and Windows computers alike. The largest part of the multimedia compendium now available (31% of the screen pages) is dedicated to the description of the symptoms of rheumatoid arthritis and examination techniques. Other main areas are pathogenesis (19%), imaging modalities (14%), differential diagnoses (11%), therapy (10%), and laboratory tests (7%). Videos and animations serve to illustrate cellular processes and to summarize the clinical examination techniques. Catalogues of established criteria for electronic media were adhered to during development to assure quality. A simultaneously performed formative evaluation yielded initial results about the practicability and stability of the program but cannot replace a thorough summative evaluation. Multimedia textbooks such as the compendium presented here are ideal supplements to classical textbooks in conventional teaching, providing a rapidly accessible knowledge base for problem-oriented training. However, the results achieved with computer-based learning tools available for optional use at teaching centers have so far lagged behind expectations. It remains to be discussed to what extent the advantages of multimedia technology can save both cost and time by being selectively integrated into the curriculum at German universities.

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Nziza, Nadege. "Le rôle des cellules myéloïdes et microARNs dans l'arthrite juvénile." Thesis, Montpellier, 2019. http://www.theses.fr/2019MONTT014/document.

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L’arthrite juvénile idiopathique (AJI) est un groupe hétérogène de rhumatismes inflammatoires chroniques affectant les enfants de moins de 16 ans. Cette atteinte inflammatoire d’origine inconnue est caractérisée par une arthrite persistant plus de 6 semaines en l’absence de traitements.Afin de mettre en évidence des mécanismes impliqués dans la physiopathologie de l’AJI, une inclusion de patients atteints d’une autre forme d’arthrite juvénile, à savoir l’arthrite septique, a été effectuée. En parallèle, des études comparatives entre le sang périphérique (SP) et le liquide synovial (LS) des patients atteints d’AJI ont été réalisées afin de rechercher des mécanismes spécifiques aux perturbations articulaires. Un intérêt particulier a été porté sur les sous-populations de monocytes et de cellules dendritiques (DCs) ainsi que les profils d’expression des microARNs (miARNs) dans le sang périphérique et le LS des patients. Ces différents marqueurs biologiques ont été choisis car ils jouent un rôle majeur à la fois dans la régulation de l’inflammation et la pathogénèse des maladies inflammatoires.L’analyse de l’expression des miARNs par une approche de séquençage à haut débit suivie d’une validation par RT-qPCR a mis en évidence des miARNs dérégulés de façon spécifique dans l’AJI par rapport à l’AS. De plus, la caractérisation phénotypique des sous-populations de cellyles myéloïdes a montré une accumulation et une activation cellulaire propre à l’AJI. Dans l’ensemble, ce projet m’a permis d’identifier différents acteurs cellulaires et moléculaires pouvant être impliqués dans la physiopathologie de l’AJI
Juvenile idiopathic arthritis (JIA) is a heterogeneous group of chronic inflammatory rheumatism affecting children under 16 years of age. This inflammatory disorder of unknown origin is characterized by arthritis lasting more than 6 weeks in the absence of treatments.In order to highlight mechanisms involved in the pathophysiology of JIA, an inclusion of patients suffering from septic arthritis, another form of juvenile arthritis, was performed. In parallel, comparative studies between the peripheral blood (PB) and the synovial fluid (SF) of patients with JIA were carried out in order to search for mechanisms specific of joint disturbances.We focused on monocytes and dendritic cells (DCs) subsets as well as the expression patterns of microRNAs (miRNAs) in the PB and SF of patients. These different biological markers are known to play a major role both in the regulation of inflammation and the pathogenesis of inflammatory diseases.Analysis of miRNA expression by a high-throughput sequencing approach followed by RT-qPCR validation revealed specifically deregulated miRNAs in JIA compared to AS. In addition, the phenotypic characterization of myeloid cell subpopulations showed an accumulation and activation profile specific of JIA cells. Overall, this project allowed me to identify different cellular and molecular actors that might be involved in the pathophysiology of JIA

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Matthee, Pierre Armand. "The quality of life of arthritis patients taking biologic arthritis medication." Diss., University of Pretoria, 2014. http://hdl.handle.net/2263/46176.

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The goal of the study was to explore and describe how arthritis patients experience the influence of arthritis on their quality of life after commencing with biologic arthritis medication. In order to achieve this goal, a qualitative research approach was adopted in an attempt to understand what the arthritis patients experience their quality of life to be while taking biologic arthritis medication. To achieve the research goal, the collective case study guided the research. Individual interviews, specifically semi-structured one-to-one interviews, with an interview schedule, were used as method of data collection. The researcher made use of Creswell’s (1998) qualitative data analysis process to analyse and to interpret the qualitative data. The trustworthiness of the data interpretation was confirmed through credibility, transferability, dependability and conformability. An analysis of the literature and transcripts of interviews was undertaken to answer the following research question: What is the influence of biologic arthritis medication on the quality of life of arthritis patients? The key findings of the study can be stipulated as follows: (1) Several signs and symptoms are associated with an arthritis patient, such as pain and fatigue; (2) Arthritis patients often visit several medical practitioners which can even be over a period of years before an official diagnosis of arthritis can be made; (3) A decrease of arthritis symptoms may be experienced during pregnancy, but increases again after the delivery; (4) Several types of arthritis treatments are available for managing the arthritis condition, ranging from traditional methods, such as anti-inflammatory medication, to biologic medication, such as Adalimumab (Humira); (5) A lack of knowledge pertaining to certain levels of medical doctors causes a mistrust amongst patients towards medical personnel; (6) Quality of life is a variable construct that is influenced by a patient’s culture and values; (7) Arthritis affects the patient’s ability to perform daily activities, such as washing; (8) Employment is important in making the patient feel human and therefore patients tend to hide their condition or to make adjustments at work, just to keep on working; (9) Biologic medication is seen as a miracle drug, albeit not totally without side effects, as patients are able to do things that were previously impossible; (10) Relationships are important in the life of an arthritis patient to enable coping, whether it be family, friends or the relationship with their medical practitioner; (11) Support provided by patients amongst themselves was also found to be important in order to facilitate coping with the disease; (12) Arthritis patients are encouraged to participate in physical exercise as it increases joint mobility; and lastly, (13) Biologic medication is quite expensive and patients are reliant on medical aids for funding of the treatment. In strengthening the role of social workers to assist arthritis patients to manage their disease better, the following recommendations are offered: (1) An awareness campaign facilitated by social workers, with experience in arthritic conditions, in collaboration with other health care workers in order to create awareness at different levels of society; (2) Social workers working in the field of arthritis should continuously strive toward improving the quality of life of arthritis patients they work with by setting up support networks and facilitating programmes that aim toward empowering those living with arthritis; (3) Social workers are encouraged to partner with rheumatology practices during which social workers are able to support newly diagnosed patients from the point of diagnosis. Social work support services could be in the form of counselling, or group support programmes; (4) A “fit for life” programme is recommended that is facilitated by social workers working with patients suffering from arthritic conditions with the goal of providing a safe environment where patients can be encouraged to be physically active. The aim will be to improve the patients’ quality of life experience, but also to create a safe environment for patients to support each other. (5) It is recommended that social workers working in the field of arthritis set up a database of patients that have proved to be involved in support programmes and shared their desire to provide guidance to newly diagnosed arthritis patients. The aim is then to partner a newly diagnosed arthritis patient with a more “senior” patient with a similar diagnosis and characteristics in order to establish a buddy support system. A context can then be created where the “senior” patient can share surviving techniques to the newly diagnosed patient but also provide assistance, for example picking up the children from school. Social workers are encouraged to then work closely with these buddies in order to provide further therapeutic support should it be required (6) Social workers working in the field of arthritis should always seek to advocate for arthritis patients when presenting at conferences and workshops (7) Investigate current, refine, or develop, policy related to the management and treatment of arthritis. Such policy should address aspects, including but not limited to, the employment conditions of people living with arthritis and securing the employment of people once diagnosed with the disease, medical aid and the requirements patients need to comply with in order to receive the full benefit provided to patients by medical aids, and thirdly, aspects related to the pricing (i.e., affordability) of disability insurance (8) The design and implementation of a continuous professional development programme is recommended to enable all health care workers to be continuously up to date with the latest developments related to arthritis research and management, in order to ensure that first line practitioners, for example physio-therapists and general practitioners, be equipped with the necessary skills to identify possible arthritis signs and symptoms which will ensure that patients are referred to specialist intervention as soon as possible. The sooner the patient receives the adequate level of care, the less joint deterioration may be sustained, and the higher the possibility to enjoy a good quality of life Future research could focus on initiating a research study that covers a more extensive geographical area, which is also more representative of the ethnic diversity in South Africa. Such a study could also cover more of the biologic medication used in the treatment of arthritis in order to reach a more holistic picture.
Dissertation (MSW)--University of Pretoria, 2014.
tm2015
Social Work and Criminology
MSW
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Vingsbo, Lundberg Carina. "Chronic autoimmune arthritis in rats pathogenesis and genetic factors /." Lund : Lund University, 1997. http://catalog.hathitrust.org/api/volumes/oclc/68945081.html.

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Gibbon, Wayne William. "Imaging in inflammatory arthritis : a multidisciplinary team approach /." [St. Lucia, Qld.], 2004. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe18870.pdf.

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Goertz, Christine [Verfasser], and Stephan [Gutachter] Meller. "Evaluation verkürzter MRT-Scores bei Patienten mit Rheumatoider Arthritis (Rheumatoid Arthritis MR Imaging Score (RAMRIS)) und Psoriasis-Arthritis (Psoriatic Arthritis MR Imaging Score (PsAMRIS)) / Christine Goertz ; Gutachter: Stephan Meller." Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2021. http://d-nb.info/1233007572/34.

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Calander, Ann-Marie. "Proteases in staphylococcal arthritis /." Göteborg : Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, Göteborg University, 2007. http://hdl.handle.net/2077/2584.

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Ulfgren, Ann-Kristin. "Cytokines in rheumatoid arthritis /." Stockholm, 2000. http://diss.kib.ki.se/2000/91-628-3823-7/.

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DeLaura, Angela. "Rheumatoid arthritis : an overview /." Online version of thesis, 1989. http://hdl.handle.net/1850/11502.

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Cruwys, Simon Charles. "Neurogenic influences on arthritis." Thesis, Queen Mary, University of London, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.243318.

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Edwards, Bryan Michael. "Collagen epitopes in arthritis." Thesis, Imperial College London, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.265003.

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Thomson, W. "Immunogenetics of rheumatoid arthritis." Thesis, University of Manchester, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.383908.

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Bodman, Katherine Birgitta. "IgG glycoforms in arthritis." Thesis, University College London (University of London), 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.283129.

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Kapoor, Sabrina Reenu. "Metabolomics of inflammatory arthritis." Thesis, University of Birmingham, 2014. http://etheses.bham.ac.uk//id/eprint/5251/.

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Background Rheumatoid arthritis (RA) is associated with both local and systemic inflammation which influences the function of the whole body as well as local tissues in the joints. Significant consequences of this are changes in metabolism. Hence, we hypothesised that chronic inflammation alters metabolism and that the metabolic profile of an individual patient with early inflammatory arthritis predicts the subsequent course of disease. Furthermore, we suggested that these metabolic changes would identify biomarkers of response to treatment in inflammatory arthritis and provide novel insights into disease mechanisms. Methods Using NMR spectroscopy of serum, urine and synovial fibroblasts we derived metabolic profiles and subjected these to multi-parameter analyses to identify metabolic differences associated with inflammation. Results We were able to predict outcome in patients with early arthritis using material derived from cultured synovial fibroblasts but were unable to do so using serum. There was a significant association between CRP levels in the patients’ serum and the metabolic profile of their synovial fibroblasts and their serum. There was also a significant association between the metabolomic fingerprint of synovial fibroblasts and the fibroblasts’ IL6 production. We found differences in metabolites between urine samples of RA and psoriatic arthritis (PsA) patients and were able to predict responses to anti-TNF therapy in patients with RA. Discussion Our results demonstrate that underlying inflammatory processes drive significant changes in metabolism that can be measured in the peripheral blood, synovial fibroblasts and urine samples in patients with inflammatory arthritis.

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Olinik, O. Yu. "Psoriatic arthritis and hyperuricemia." Thesis, БДМУ, 2022. http://dspace.bsmu.edu.ua:8080/xmlui/handle/123456789/19621.

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Kalla, Asgar Ali. "Osteoporosis in rheumatoid arthritis." Master's thesis, University of Cape Town, 1989. http://hdl.handle.net/11427/26297.

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The literature is replete with reports of osteoporosis in rheumatoid arthritis, but the mechanism of bone loss remains obscure. This is probably due to the overlap with bone loss of aging and the menopause, whose exact mechanisms are also poorly understood. Against this background, a study was designed to evaluate generalised bone loss in young, premenopausal (if female), patients with rheumatoid arthritis. The protocol was designed to record demographic data, as well as information pertaining to the disease. Cortical bone mass was measured at the metacarpals and left femur, using an automated, computer-controlled technique. Trabecular bone was evaluated at the left femur (Singh index) as well as at the 3rd lumbar vertebra (Saville index). Bone kinetics were studied by the measurement of urinary excretion of calcium, phosphate and hydroxy-praline (resorption) and serum alkaline phosphatase (formation). Disease activity was measured clinically and with laboratory indices. Physical activity was indirectly measured by quantitating the disability, using the Keitel function test as well as a modified health assessment questionnaire (HAQ). The radiograph of the right wrist was scored by the Larsen index. The carpometacarpal ratio was also calculated from the radiograph. Numerous statistical techniques were applied in the analysis of the data. Healthy volunteers were used as controls. Patients with SLE were also studied, in order to compare the 2 inflammatory diseases. Patients with RA had generalised cortical bone loss (metacarpal and femur) (p < 0.001). Trabecular bone measurements were not significantly different from normals, using the crude radiographic techniques. Duration of disease was the most important clinical determinant of this bone loss. The relative contributions of disease activity and lack of physical activity to the loss of bone could not be adequately separated using conventional statistical techniques. Corticosteroid therapy did not promote metacarpal bone loss in these subjects, but may have contributed to thinning of the femoral cortex. Nonsteroidal anti-inflammatory drugs and disease modifying agents did not seem to influence the extent of the bone loss. Nutritional status and skinfold thickness did not correlate with bone mass. Dietary factors played no role in the genesis of bone loss, but may have had some effect on disease activity. Metacarpal measurements showed a sensitivity of 80% and specificity of 85% in discriminating between osteopaenic and normopaenic groups with RA. Osteopaenia could not be adequately predicted in the absence of metacarpal measurements. Metacarpal bone loss in RA was due to endosteal resorption, while in SLE it was due to periosteal resorption. The semi-automatic technique for measurement of metacarpal bone mass showed good reproducibility among 5 observers and at 2 different centres. The pathogenesis of bone loss in RA was multifactorial, the largest contribution probably coming from a humoral factor in the circulation, closely related to disease activity. Ionised calcium was elevated in 55% of RA patients, but only 5% of SLE patients. Serum PTH levels were normal in 99% of the RA subjects. Elevations in alkaline phosphatase. (25%) probably reflected disease activity rather than increased bone formation. Factor analysis of 27 variables showed that disease activity was central to the development of OP in RA. CS therapy tended to be used in the presence of active disease. Disability was not an important determinant of bone loss in RA, but may be a useful measure of activity of the disease. This study did not evaluate the relationships with sex hormonal status or vitamin D metabolism. Future research should aim at cohort analysis at 2 different periods, in order to improve our understanding of the pathogenesis of bone loss in RA.

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Toms, Tracey. "Dyslipidaemia in rheumatoid arthritis." Thesis, University of Manchester, 2012. https://www.research.manchester.ac.uk/portal/en/theses/dyslipidaemia-in-rheumatoid-arthritis(e7808bd7-52e6-40a0-84cb-e4aadbf7505c).html.

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Introduction: Rheumatoid arthritis (RA) is known to be associated with an increased risk of cardiovascular disease (CVD), resulting in excess mortality. Dyslipidaemia has been identified as a major CVD risk factor in the general population. Current evidence would suggest that lipid metabolism is altered in RA due to inflammation, and that use of anti-inflammatory therapy may reverse some of these changes. However, the impact of such lipid changes on CVD in RA remains unknown. Data regarding the effects of RA/drug therapy on lipid structure and function are sparse. Genetic factors are important in the pathogenesis of RA and play a central role in the regulation of lipid metabolism. To date, no studies have assessed the impact of genetic polymorphisms on lipids in RA.The aim of this thesis is to: 1) assess the prevalence of dyslipidaemia in RA and the CVD risk this confers 2) establish the effects of inflammation on lipid levels and lipid ratios 3) assess the impact of anti-inflammatory drug therapy (anti-TNF, rituximab and intravenous glucocorticoids) on lipid levels, structure and function 4) assess the prevalence and associations of particular genetic polymorphisms (RA susceptibility and lipid metabolism regulating genes) with lipids in RA.Methods: Data from 400 RA patients were used to address aims 1, 2 and 4 in cross-sectional studies. All patients had a clinical assessment and fasting blood taken. Blood was processed to provide data on the lipid profile, ESR, CRP and DNA was extracted for genotyping. Aim 2 and 4 also utilised a retrospective longitudinal cohort of 550 RA patients and the DNA from 400 healthy controls, respectively. Aim 3 was addressed using a longitudinal cohort including: patients due to commence anti-TNF (n=35), rituximab (n=10), intravenous glucocorticoids (n=12); 15 RA controls on stable therapy; and 40 healthy controls. Assessments and blood samples were taken at baseline, 2 weeks and 3 months. Results: Dyslipidaemia was highly prevalent (56.8%), but undertreated in many RA patients at risk of developing CVD. Systemic inflammation associated with many of the changes in lipid levels and structure. Lipid ratios were found to be less susceptible to fluctuations due to inflammation. The use of anti-inflammatory drug therapy produced changes in lipid structure and function through both generic suppression of inflammation and drug specific mechanisms (particularly in the case of glucocorticoids). The prevalence of cholesterol ester transfer protein (CETP) and Apolipoprotein C3 genetic polymorphisms differed between RA patients and local population controls. RA susceptibility genes (HLA-DRB1-SE and TRAF1C5) and several ’lipid metabolism genes’ (Apolipoprotein E, ATP-binding cassette transporter 1 (ABCA1) and CETP) were found to associate with lipid levels within the RA population. Conclusion: Dyslipidaemia is highly prevalent in RA and currently undertreated. Dyslipidaemia in RA is regulated by numerous factors including inflammation, drug therapy and genetic factors. Further longitudinal studies are required to assess whether these findings have an impact on hard CVD endpoints.

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Courties, Gabriel. "Développement d'Immunothérapies anti-inflammatoires de la polyarthrite rhumatoïde par ARN interférence dans un modèle murin d'arthrite." Thesis, Montpellier 1, 2010. http://www.theses.fr/2010MON1T016.

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La polyarthrite rhumatoïde (PR) est le plus fréquent des rhumatismes inflammatoires et représente un problème de santé publique majeur. A l'heure actuelle, les biothérapies anti-TNF sous forme de protéines recombinantes constituent une avancée considérable dans le traitement de la polyarthrite rhumatoïde (PR). Néanmoins, il convient de développer des approches thérapeutiques alternatives pour traiter les 40% de patients non-répondeurs ainsi queceux qui échappent à plusieurs années de traitement. La recherche de nouvelles cibles thérapeutiques est indispensable pour proposer des approches alternatives à ces biothérapies. Par ailleurs, les techniques de transfert de gène offrent une alternative thérapeutique possible pour pallier aux limitations des biothérapies actuelles, à condition de les adapter aux contraintes du tissu cible de la PR, les articulations. Les projets ont consisté à développer et valider dans des modèles expérimentaux d'arthrite de nouvelles stratégies anti-inflammatoires basées sur l'utilisation de l'ARN interférence comme outil thérapeutique. En effet, la possibilité d'interférer au niveau des mécanismes responsables de l'expression des protéines,la régulation de la stabilité des ARNm et de l'efficacité de la machinerie traductionnelle, présente un intérêt thérapeutique supérieur aux biothérapies actuelles basées sur l'inhibition des protéines sécrétées (anticorps ou récepteurs solubles) mais nécessite cependant de posséder un vecteur qui transduit efficacement les cellules productrices de la molécule ciblée
Rheumatoid arthritis (RA) is the most frequent chronic inflammatory systemicautoimmune disease that remains a major medical challenge as the exact causes of the disease are not completely elucidated. The principal treatment strategies arebased on the inhibition of TNF-α, one of the major inflammatory cytokine in RA.Although risk and benefit analyses are in favour of the use of monoclonal antibodiesagainst TNF-α, the most currently used biotherapy, they are not devoid from multipleside effects. The search for new therapeutic targets is essential to proposealternative approaches to non responders to such biotherapies. The possibility to interfere in the mechanisms responsible for regulating mRNA stability andeffectiveness of the translational machinery also present a therapeutic benefitsuperior to current biologic therapies based on inhibition secreted proteins(antibodies or soluble receptors). Such approach however requires developingvectors that efficiently transduced the specific cell type producing the targeted gene.Projects of my PhD fellowship have included both the development of gene therapyvehicles for RNAi-based intervention in experimental mouse models of arthritis andevaluation of novel candidate genes for alternative anti-inflammatory therapy in RA

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Holm, Barbro. "Pathogenetic studies of adjuvant-induced arthritis /." Stockholm, 2002. http://diss.kib.ki.se/2002/91-7349-347-3/.

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Roy, Josée. "Stratégies d'adaptation à l'arthrite chronique chez les octogénaires." Sherbrooke : Université de Sherbrooke, 2002.

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43

Hawtree, Sarah. "Investigation of the roles of histone deacetylases in rheumatoid arthritis and collagen-induced arthritis." Thesis, University of Sheffield, 2015. http://etheses.whiterose.ac.uk/10169/.

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Rheumatoid arthritis (RA) is a chronic, autoimmune, inflammatory disease that affects synovial joints. A key characteristic of RA is hyperplasia of fibroblast-like synoviocytes (FLS) which develop a stable, auto-aggressive phenotype that augments tissue destruction. It is unknown how this phenotype is stably maintained; however, epigenetic changes have been implicated. Histone deacetylation is one proposed method; a process controlled by histone deacetylases (HDACs). However, there have recently been reports publishing conflicting data regarding the expression of HDACs in RA synovium and FLS. The objective of this thesis is to determine the role of HDACs in regulating the auto-aggressive phenotype of RA through studies in FLS and in mice. Real time-quantitative PCR was used to assess the levels of HDAC1-11 in RA compared to osteoarthritis (OA) FLS. Immunohistochemistry and western blotting were used to assess protein expression of HDAC1 in RA and OA synovial tissue and FLS. HDAC1 was found to be overexpressed in RA compared to OA. HDAC1 was knocked down in RA FLS, then cell proliferation, migration and invasion were assessed by using tritiated thymidine, a scratch assay and a Matrigel invasion assay respectively. All three functions were significantly reduced following HDAC1 knockdown. An Illumina BeadChip (47,000 transcripts) was used to analyse global gene expression changes after knockdown. This revealed significant gene changes in important functional clusters, such as proliferation and migration. HDAC1 knockout is embryonic lethal in mice, so the in vivo role of HDAC1 was investigated in a mouse model of collagen-induced arthritis (CIA) using in vivo siRNAs. Clinical scores of CIA were measured daily and HDAC1 knockdown mice showed a significantly reduced clinical score compared to controls, comparable to dexamethasone-treated mice. The bones were analysed using a microCT scanner and histology. Knocking down HDAC1 showed reduced bone erosion, joint inflammation and cartilage degradation compared to controls. Overall, this study shows that HDAC1 is dysregulated in RA and it has a significant role in the autoaggressive phenotype shown in RA FLS and collagen-induced arthritis. The novel data shown in this thesis demonstrates that inhibiting HDAC1 may provide a powerful new target for treating RA.

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Courbon, Guillaume. "Etudes cinétiques de la perte osseuse au cours de l'inflammation articulaire chronique." Thesis, Lyon, 2016. http://www.theses.fr/2016LYSES053.

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La polyarthrite rhumatoïde est un rhumatisme inflammatoire chronique qui s’accompagne d’une inflammation synoviale et d’une perte osseuse sous-chondrale. Ces travaux de thèse ont porté sur la perte osseuse précoce dans l’arthrite et les mécanismes osseux et inflammatoires associés. La perte osseuse systémique a été étudiée et mise en relation avec la perte osseuse locale. La preuve de concept d’une perte osseuse précoce a été obtenue dans plusieurs études. Cette perte prédisait la sévérité de l’arthrite et débutait avant l’observation clinique de l’inflammation articulaire. Elle se traduisait par des modifications de la microarchitecture de l’os cortical et trabéculaire. Les mécanismes associés impliquaient l’activation de la résorption osseuse mais également l’inhibition de la formation osseuse. Une perte osseuse systémique a aussi été détectée, corrélant avec la perte locale. Dans le modèle de souris avec expression chronique du tumor necrosis factor (TNF), la perte osseuse axiale résultait d’une augmentation de la résorption osseuse sans affecter l’activité des ostéoclastes, suggérant que l’inhibition du TNF expliquerait la ré-ossification dans les formes axiales de SpA. L’infection orale avec Porphyromonas gingivalis induisait en huit mois une arthrite à bas bruit chez le rat, en augmentant les anticorps anti-peptides citrullinés et la résorption osseuse. Sur le versant translationnel, deux candidats thérapeutiques de l’arthrite ont démontré un effet régulateur de la dégénérescence articulaire associé à un effet protecteur sur l’os sous-chondral. Les résultats obtenus renforcent le concept de perte osseuse précoce dans l’arthrite, avec l’implication rapide des voies de régulations du tissu osseux. Des stratégies de bloquage de la résorption et de l’inhibition de la formation osseuse pourraient ainsi être développées dans les rhumatismes inflammatoires chroniques et leur usage envisagé dès les premiers stades de maladie
Rheumatoid arthritis is a chronic inflammatory joint disease which is accompanied by synovial inflammation and subchondral bone loss. This thesis focused on early bone loss in arthritis and bone-associated inflammatory mechanisms. The preclinical stages of arthritis have been investigated through animal models. Systemic bone loss was studied and correlated to local bone loss. Proof of concept for early bone loss was obtained in several studies. This loss predicted arthritis severity and started before clinical observation of joint inflammation. Early bone loss was associated with cortical and trabecular bone microarchitecture changes. Associated mechanisms involved at the same time the activation of bone resorption and the inhibition of bone formation. A systemic bone loss was also detected, correlating with the local loss. In the mouse model with chronic expression of tumor necrosis factor (TNF), axial bone loss resulted from an increase in bone resorption without affecting osteoclast activity, suggesting that inhibition of TNF explain the re-ossification in axial forms of SpA. Oral infection with Porphyromonas gingivalis induced systemic arthritis in rats over eight months, increasing citrullinated anti-peptide antibodies levels and bone resorption. In a translational approach, two therapeutic candidates for arthritis treatment have shown regulatory effects on joint destruction associated with a protective effect on the subchondral bone. These results reinforced the concept of early bone loss in arthritis, with the involvement of osteoimmune signalling. Blockade strategies of bone resorption and bone formation inhibition might be developed in the chronic inflammatory joint diseases, and their use might be considered in the early stages of disease

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Koufany, Meriem. "Étude de la contribution des récepteurs activés par les proliférateurs de peroxysomes en physiopathologie articulaire." Thesis, Université de Lorraine, 2015. http://www.theses.fr/2015LORR0230/document.

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Les récepteurs activés par les proliférateurs de peroxysomes (PPARs) sont des facteurs de transcription impliqués dans la régulation du métabolisme lipidique et de la tolérance au glucose. Les PPARs contrôlent également l’inflammation associée à de multiples pathologies, dont la polyarthrite rhumatoide. Dans les travaux présentés dans ce manuscrit, nous avons comparé les potentialités anti-arthritiques, dans un modèle expérimental, de deux agonistes synthétiques de haute affinité pour deux isotypes de PPARs, PPARα et PPARγ. Nous avons démontré qu’un traitement avec un agoniste sélectif de PPARγ, la pioglitazone, en plus de diminuer la sévérité de l’arthrite expérimentale, réduisait la perte osseuse inflammatoire en préservant la micro-architecture osseuse. Nous avons mis en évidence que PPARγ, d’une part, régulait l’expression locale et systémique de l’interleukine-17 et de RANKL, et que, d’autre part, il inhibait l’expression du facteur de transcription RORγt, acteur majeur de la voie IL-17/Th17. Les animaux déficients pour PPARγ nous ont permis de confirmer son rôle majeur dans le développement du processus arthritique. En effet, ces animaux présentent tous et de façon spontanée une arthrite associée à une augmentation du nombre de mastocytes capables de produire l’IL-17 et leur propre facteur de différenciation, le SCF dans la synoviale inflammatoire. Enfin, nous avons discuté le lien possible entre l'arthrite inflammatoire et la mastocytose à la lumière de l’étude d’un cas clinique d’un patient atteint de polyarthrite rhumatoïde concomitante à une mastocytose systémique
Peroxisome proliferator-activated receptors (PPARs) are transcription factors implicated in lipid metabolism and glucose tolerance. Once activated by specific agonists, PPARs control inflammation associated with numerous diseases, notably Rheumatoid arthritis. The first study presented here aim to compare the anti-arthritic potency of two high-affinity synthetic agonists for PPARα and PPARγ in an experimental model. Then we focused on the effect of pioglitazone, a high-affinity synthetic agonists for PPARγ, and demonstrated that a per os treatment with this agonist not only reduced experimental arthritis but also inhibited partly inflammation-related bone loss by preserving bone microarchitecture. We pointed out that PPARγ, on one hand, regulated local and systemic expression of interleukine-17 (IL-17) and RANKL and on the other hand, inhibited expression of transcription factor RORγt, a main regulator of IL-17/Th17 pathway. Study of mice deficient for PPARγ confirmed its major role in the development of the arthritic process since these mice developed spontaneously arthritis. Of interest arthritis in these mice is associated with increased number of synovial mast cells able to produce IL-17 and their own differenciation factor, the SCF. Finally, we discussed the possible link between inflammatory arthritis and mastocytosis in a case report of a patient suffering from rheumatoid arthritis concomitant to systemic mastocytosis

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Iaquinta, Monica L. "The phenomenological lived experience of rheumatoid arthritis." Morgantown, W. Va. : [West Virginia University Libraries], 2001. http://etd.wvu.edu/templates/showETD.cfm?recnum=1842.

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de, Souza Patricia Regina Soares. "GPR40 expression and function in immune cells and experimental arthritis." Thesis, Queen Mary, University of London, 2017. http://qmro.qmul.ac.uk/xmlui/handle/123456789/25975.

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Omega-3 fatty acids (ω-3 FA, including eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]), are essential polyunsaturated fatty acids which are correlated with lower incidence of chronic diseases. DHA and EPA can be enzymatically converted to resolvins, protectins and maresins, which play important roles in resolution of inflammation. Additionally, ω-3 FA can also directly activate surface receptors, namely the long-chain free fatty acid receptors GPR40 and GPR120, two GPCRs with poorly investigated biology. Using real-time PCR analysis, GPR40 transcript in human neutrophils was detected; the protein expression was also confirmed by flow cytometry and image stream analysis. Expression of GPR40 protein was up-regulated after stimulation with platelet-activating factor (PAF, 10nM) or leukotriene B4 (LTB4, 10nM) for 10 minutes. I utilised the selective agonist GW9508 to investigate the biology of GPR40. Tested on human neutrophils, GW9508 elevated intracellular calcium when applied within the 0.1-10μM range. The up-regulation of GPR40 expression by pro-inflammatory stimuli suggested to us potential regulatory roles for this receptor during inflammation. I then showed that 1 and 10μM GW9508 increased neutrophil chemotaxis in response to the cytokine IL-8 (30ng/ml). In addition, GPR40 activation by GW9508 enhanced phagocytosis of E. coli by human neutrophils by approximately 50% when tested at 0.1 and 1μM. Moreover, GW9508-neutrophil stimulation augmented microvesicle release and delayed apoptosis after stimulation. Finally, I demonstrated that GPR40 is expressed in inflammatory cells isolated from murine arthritic joints, such as neutrophils, macrophages and inflammatory monocytes. KBN-serum induced arthritic mice developed a more severe disease when treated prophylactically with GW9508 (10mg/kg, i.p. treated from day 0, daily), characterized by a higher clinical score and increased oedema when compared to vehicle control mice. Therapeutic intervention with GW9508 at the peak of the disease (day 5) delayed the resolution of arthritis. In summary, the data suggest that activation of GPR40 by GW9508 enhances neutrophil activation, up regulating the pro-inflammatory properties of this cell type, and therefore, exacerbating experimental inflammatory arthritis.

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48

Fabre, Annie-Claude. "Notre expérience sur les arthrites septiques des membres : à propos de 58 observations." Bordeaux 2, 1992. http://www.theses.fr/1992BOR2M171.

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49

Schumann, Frank. "Autoantigene bei der rheumatoiden Arthritis." [S.l.] : [s.n.], 2004. http://www.diss.fu-berlin.de/2004/199/index.html.

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50

Schnez, Amelie. "Standardisierte Gelenkuntersuchung bei rheumatoider Arthritis." Diss., lmu, 2012. http://nbn-resolving.de/urn:nbn:de:bvb:19-142212.

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Dissertations / Theses on the topic 'Arthriti'

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