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Grandon, Benjamin. "La drosophile transgénique HLA-B27 : un nouveau modèle pour l'étude des spondyloarthrites". Thesis, Université Paris-Saclay (ComUE), 2018. http://www.theses.fr/2018SACLV051/document.
Pełny tekst źródłaSpondyloarthritis (SpA) is a chronic inflammatory rheumatic disorder characterized by joint manifestations affecting the spine, peripheral joints and entheses, as well as extra-articular manifestations such as psoriasis, uveitis, or intestinal inflammation. This complex disorder has a strong genetic component dominated by the HLA-B27 antigen of the major histocompatibility complex class I (MHC-I), which is present in more than 80% of SpA patients. Discovered 45 years ago, the association between HLA-B27 and SpA development remains unexplained. Several hypotheses have been proposed to explain this association at the molecular level, but all face experimental inconsistencies that seem to invalidate them. Therefore, it appeared to us essential to elaborate new and yet unexplored approaches in order to better understand the molecular role of HLA-B27 in SpA development. Drosophila melanogaster is a powerful genetic model that has led to considerable advances in understanding numerous functions of metazoan cells, as well as in describing the cellular and molecular processes of many human pathologies. To elucidate the molecular pathogenic mechanisms associated with HLA-B27, we have established several transgenic Drosophila lines for SpA-associated and non-associated of HLA-B alleles, as well as for the MHC-I invariant chain, the human 2-microglobulin (hβ2m). Expression of the HLA-B27 alleles, in the presence of hβ2m, in the Drosophila wing and eye led to two specific phenotypes. The crossveinless wing phenotype is due to a disturbance in the Bone Morphogenetic Protein (BMP) signaling pathway. Interestingly, this misregulation is associated with a co-localization of HLA-B27 and the BMP type I receptor named Sax. Our preliminary results obtained in SpA patient cells suggest that HLA-B27 also colocalizes with ALK2 receptor, which is ortholog to Sax. Altogether, our results suggest that the pathogenic role of HLA-B27 in SpA may depend on a BMP signaling misregulation at the crosstalk between ossification and inflammation
Miralles, Daniel. "Troubles de l'avant-pied dans les spondylarthropathies". Montpellier 1, 1989. http://www.theses.fr/1989MON11184.
Pełny tekst źródłaLauraine, Marc. "Effets d'HLA-B27 sur la voie BMP/TGFbeta dans les lymphocytes T CD4+, dans le contexte de la spondyloarthrite". Electronic Thesis or Diss., université Paris-Saclay, 2023. http://www.theses.fr/2023UPASL130.
Pełny tekst źródłaSpondyloarthritis (SpA) is a common chronic inflammatory disease. In human, the association between the HLA-B27 allele of the class-I major histocompatibility complex (MHC-I) and the development of this disease was demonstrated 50 years ago, with 70-90% of SpA patients carrying this allele. However, the exact role of HLA-B27 in the pathophysiology of SpA remains unknown. The model of rat transgenic for HLA-B27 and the human β2-microglobulin (hβ2m) (B27 rat), which develops manifestations similar to the human disease, has shed light on certain aspects of the question. In particular, the involvement of CD4+ T lymphocytes in SpA has been demonstrated. In the B27 rat, regulatory CD4+ T lymphocytes (Treg) exhibit an imbalance of the interleukin-10/interleukin-17 (IL-10/IL-17) ratio, which are anti-inflammatory and pro-inflammatory, respectively. On the other hand, an expansion of the sub-population of pro-inflammatory CD4+ T helper 17 (lymphocytes Th17), which produce IL-17, was observed in both B27 rats and SpA patients. To study the non-canonical effects of HLA-B27, a Drosophila melanogaster model transgenic for HLA-B27 and hβ2m was developed and demonstrated that an interaction between HLA-B27 and type I receptors of the BMP/TGFβ pathway (BMPR1s) altered the formation of the wing transverse veins. In this model, an interaction between HLA-B27 and the Saxophone (Sax) receptor has previously been shown to lead to increased BMP signalling. Our study complemented these results by showing that aberrant signaling via the BMPR1 Baboon (Babo) of the activin/TGFβ pathway also contributed to the abnormal phenotype induced by HLA-B27 expression. In an attempt to extrapolate these results to a mechanism of HLA-B27 pathogenicity in SpA, we first demonstrated that there was a specific interaction between HLA-B27 and activin receptor-like kinase 2 (ALK2), the orthologue of Sax, and also with ALK5, the type 1 receptor for TGFβ orthologue of Babo, in rat B27 lymphocytes. Study of SMAD2/3, the main transducer of the TGFβ signal, in T lymphocytes from B27 and nontransgenic rats revealed a lower basal phosphorylation and a higher amplitude of phosphorylation after stimulation by TGFβ1. Concordantly, we observed that several genes induced by TGFβ signaling and involved in Treg and Th17 differentiation (Foxp3, Rorc, Runx1) had increased expression in naive CD4+ T lymphocytes (Tn) from B27 rats. Taken together, these results indicate a possible early activation of the TGFβ pathway in B27 rat Tn followed by a negative feedback loop. Interestingly, the Tgfb1 gene itself was decreased. Given the importance of autocrine TGFβ1 produced by T lymphocytes in preventing chronic inflammation, these observations open up prospects for a better understanding of the role of HLA-B27 in the development of SpA. In particular, we propose to study in greater depth the response of Tn from B27 rats to TGFβ1 using multi-omics methods (transciptomic, phosphoproteomic, proteomic). Finally, given the essential role of autocrine TGFβ1 in the maintenance of Treg and Th17 profiles, a study of the plasticity of Treg and Th17 in B27 rat would be relevant to a better understanding of the pathophysiology of SpA
Rupp, Paul-Antoine. "Spondylarthropathie destructive découverte par une paraplégie progressive chez un patient dialysé depuis 12 ans, évolution favorable aprés chirurgie". Bordeaux 2, 1993. http://www.theses.fr/1993BOR2M119.
Pełny tekst źródłaMambu, Mambueni Hendrick. "Identification de nouveaux variants rares associés à la spondyloarthrite par séquençage haut-débit". Electronic Thesis or Diss., université Paris-Saclay, 2022. http://www.theses.fr/2022UPASL064.
Pełny tekst źródłaSpondyloarthritis (SpA) is a multifactorial disease with an estimated heritability of over 90%, mainly related to HLA-B27. All identified susceptibility factors, including HLA-B27, explain less than one third of the heritability. The involvement of rare variants could explain part of this missing heritability. The aim of this work was to identify rare variants associated with SpA via a combined family analysis and high-throughput sequencing approach. First, we sequenced a 1.4 Mb region significantly linked to SpA at 13q13 in 71 patients and 21 healthy controls from families with a high linkage score in this region. We identified a rare variant in the FREM2 gene present in 9 patients from a family with high linkage to the region and not found in other families or isolated cases of SpA. We then sequenced the exome of 48 patients from 20 multiplex families. Unfortunately, we did not observe any recurrent variants between families. We then focused on a second, previously known genetic linkage peak on chromosome 9. The study of the family most linked to this region, which includes 12 patients, led to the identification of several rare coding variants segregating with the disease. However, subsequent studies have shown equivalent allelic frequencies of these variants between cases and controls. Finally, whole genome sequencing of 413 patients from 76 multiplex families with 4 or more patients was performed. We identified 1203 rare, coding, non-synonymous variants shared by at least all affected family members. Genetic and functional validation analyses of these variants are underway, as is the analysis of non-coding variants. In conclusion, these different approaches suggest significant genetic heterogeneity in SpA and also highlight the difficulty of confirming the involvement of rare variants in complex diseases
Chaplais, Emmanuel. "Une approche de modélisation de biologie des systèmes sur la spondylarthrite". Thesis, Versailles-St Quentin en Yvelines, 2015. http://www.theses.fr/2015VERS035V/document.
Pełny tekst źródłaSpondyloarthritis is a frequent chronic inflammatory rheumatism, with a prevalence of 0.43 % in France. This disease presents axial skeleton injuries, but also on peripheral joints, and can results in a total spinal and sacro-iliac motility loss. Extra-articular features including uveitis, psoriasis and inflammatory bowel disease are frequent. Current SpA treatments are only symptomatic, relieving inflammatory symptoms. SpA etiology is largely multifactorial with a genetic component dominated by the long-known strong association with the HLA-B27 allele. This allele, however, is not sufficient for the disease to occur. This thesis project objective was then to identify other genetic factors in the origin of SpA.My work was mainly divided in two complementary data analyses, in a way to get a systems biology approach. The first one consisted in proceed linking analyses on data from Affymetrix genotyping chips gathered from DNA of 1310 people grouped in 210 families. This study allowed notably to detect a new significantly linked region to SpA : 13q13, with an interval of 1.3 Mb. This part of genome is currently being sequenced to allow a better causal SNP identification.Secondly, an Affymetrix HumanGene 1.0 st transcriptomic chips analysis was performed on MD-DCs extracted from 68 people, stimulated or not by LPS during 6 or 24 hours. This cohort was grouped between 23 patients HLA-B27+, 23 healthy controls HLA-B27+ and 21 healthy controls HLA-B27-. I could notice that HLA-B27 allele is farly enough to considerably affect cell transcriptomic profiles, which encourages to include HLA-B27+ healthy controls. Otherwise, a gene network analysis allowed me to highlight on an inhibition of early steps of cholesterol biosyntthesis
Al-Mossawi, Mohammad Hussein. "Pathogenic immune responses in spondyloarthritis". Thesis, University of Oxford, 2016. https://ora.ox.ac.uk/objects/uuid:eab12909-6af6-4269-85de-69fa99d11af7.
Pełny tekst źródłaHaibel, Hildrun [Verfasser]. "Therapie der axialen Spondyloarthritis / Hildrun Haibel". Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2015. http://d-nb.info/1075757673/34.
Pełny tekst źródłaEl, Jamal Alaeddine. "Implication du métabolisme de la sphingosine 1-phosphate dans les mécanismes biochimiques et cellulaires de la minéralisation dans la spondylarthrite ankylosante". Thesis, Lyon, 2019. http://www.theses.fr/2019LYSE1169.
Pełny tekst źródłaSpondyloarthritis (SpA) is a rheumatic disease characterized in particular by enthesis ectopic ossification and inflammation. Enthesis is a zone of concentration of mechanical stresses where ligaments and tendons attach to bone through fibrocartilaginous connections. Sphingosine 1-phosphate (S1P) is a bioactive lipid that plays an important role in both bone remodelling and in inflammatory response. Our aim was to explore the role of S1P in SpA excessive ossification. We observed that serum S1P concentrations in SpA patients are significantly higher compared to control donors. We used primary mouse osteoblasts, chondrocytes and tenocytes as cellular models and organotypic cultures of mice enthesis. We observed that S1P synthetizing enzymes, sphingosine kinases 1 and 2, stimulate osteoblasts’ and chondrocytes’ mineralizing process. S1P pro-mineralizing effect was partially mediated by two of the S1P receptors (S1P1 and S1P3). Moreover, S1P production was enhanced by cyclic strain in osteoblasts and chondrocytes and by pro-inflammatory cytokines (TNF-α and IL-17) in chondrocytes. Finally, the inhibition of S1P metabolic pathway by Fingolimod reduced the mineralization in cultured osteoblasts and even more in chondrocytes. These results suggest that S1P metabolism participates in SpA excessive ossification. In vivo studies are now needed to validate this possibility
Jarvis, Lorna Beth. "Autoreactive CD8+ regulatory T cells in spondyloarthritis". Thesis, University of Cambridge, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.605067.
Pełny tekst źródłaRidley, Anna Louise. "T cell phenotype and function in Spondyloarthritis". Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:1f3f6651-68f8-4bfa-89ee-15bb6d279ed3.
Pełny tekst źródłaPrada, Pierre. "Apport de la spectroscopie vibrationnelle dans l'analyse plasmatique outissulaire, application en pathologies : spondyloarthrite, maladie de Crohn et cancer colorectal". Electronic Thesis or Diss., Reims, 2022. http://www.theses.fr/2022REIMP201.
Pełny tekst źródłaThe search for new generation markers is crucial for better patient management, both in terms of diagnosis and prediction of treatment response. Contrary to standard approaches targeting a specific molecular target, vibrational spectroscopy techniques give access to the global molecular constitution of a sample. The work of the BioSpecT unit has shown that these techniques can provide information on tissue organization that is complementary to conventional histology. For example, spectral imaging analysis of tissue samples from cancerous lesions (colon, skin, lung) can highlight the heterogeneity of tumor zones and finely characterize the stroma. An inflammatory component can also be distinguished from other structures. The objective of this thesis project is to exploit the information available by vibrational spectroscopy in the context of pathologies specific to the colon, in order to extract numerical markers charac terizing the physiopathological state of the lesions studied. The identification of such markers requires the comparison of spectroscopic data with clinical, histological, biological or pharmacological reference information. More precisely, we will focus on metastatic colon cancers with the objective of identifying predictive markers of response to chemotherapy. For the analyses, we will be able to benefit not only from human tissue samples (tumor library of the Reims University Hospital) but also from xenografts performed in mice in order to have material obtained according to more standardized protocols. In a complementary way, part of the research work could be carried out within the framework of a study on chronic inflammatory bowel diseases, by focusing the experiments on the characterization of inflammation by vibrational spectroscopy. This research will be carried out in collaboration with the Digestive Oncology Department (Pr O Bouché) of the Reims University Hospital, the Biopathology Laboratory (Pr A Marchal) of the Reims University Hospital and the INSERM U1113 IRFAC unit (Dr D Guenot) of Strasbourg
Bazin, Thomas. "Microbiote intestinal et inflammation : prédiction de la réponse aux anti-TNFα dans les maladies inflammatoires chroniques et modulation de la croissance bactérienne in vitro en réponse au TNFα". Thesis, Bordeaux, 2018. http://www.theses.fr/2018BORD0285/document.
Pełny tekst źródłaThe host/gut microbiota interface is a system of complex interactions whose imbalance is associated with the development of chronic inflammatory diseases. Anti-TNFα treatments are very effective in these diseases, but only in some patients. The purpose of this work was to find a link between the composition of the intestinal microbiota and clinical response to anti-TNFα treatments in two types of chronic inflammatory diseases, spondyloarthritis and inflammatory bowel disease. We found variations in the composition of the intestinal microbiota after treatment with anti-TNFα in patients with spondyloarthritis and identified a taxonomic node predictive of the therapeutic response at 3 months. This taxonomic node, the Burkholderiales order, being a biomarker potentially usable in clinical practice, we have filed a European patent application, which is currently under investigation. This work was continued by a new clinical research protocol including patients with spondyloarthritis but also with inflammatory bowel diseases. This protocol is funded by the Bordeaux University Hospital as part of the internal call for tenders. It will validate the hypotheses of our first work, notably by performing quantitative PCRs using specific primers targeting the order of Burkholderiales. In vitro, we have also found for the first time, to our knowledge, a modulation of bacterial growth in Bacteroides fragilis in response to human TNFα
McHugh, Kirsty Anne. "The role of HLA-B27 in the pathogenesis of spondyloarthritis". Thesis, University of Oxford, 2011. http://ora.ox.ac.uk/objects/uuid:d7df3150-9dcb-44fe-88a0-9fd54fe94b14.
Pełny tekst źródłaSilvestri, Ylenia <1990>. "The role of CD8+CCR4+ T-cells in axial spondyloarthritis". Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2019. http://amsdottorato.unibo.it/9108/1/silvestri_ylenia_tesi.pdf.
Pełny tekst źródłaErmoza, Kétia. "Les cellules dendritiques XCR1+ dans un modèle expérimental de spondyloarthrite". Electronic Thesis or Diss., Université Paris-Saclay (ComUE), 2018. http://www.theses.fr/2018SACLV052.
Pełny tekst źródłaSpondyloarthritis (SpA) is a chronic inflammatory disease affecting primarily axial and peripheral joints and sometimes also extra-articular organs, such as the gut. Rats transgenic for HLA-B27 and human β2-microglobulin (B27-Tg rat) develop clinical manifestations resembling human disease. In this model, it has been shown that CD103+ conventional dendritic cells (cDCs) exhibited altered functions, likely promoting SpA development. CD4- cDCs sub-population expressing XCR1, a chemokine receptor involved in their migration have been described to be tolerogenic. Thus, in this study, we wished to examine the fate of XCR1+ cDCs in this animal model of SpA.cDCs populations were isolated from the spleen, mesenteric lymph nodes (MLN) and colonic lamina propria from B27-TG and control nontransgenic (NTG) and/or HLA-B7 transgenic rats after collagenase digestion and density gradient and characterized by flow cytometry or real time PCR. Migration of cDCs from intestinal mucosa to MLN was assessed, using stimulation of TLR-7 with Resiquimod. Interestingly, we observed a reduced frequency of CD4- DC in B27-Tg rats, as compared to NTG rats. Furthermore, this decrease was not due to excessive death of CD4- DCs in B27 rats. Interestingly, we observed a decreased frequency of the XCR1+ subpopulation among CD4- cDCs in the spleen, MLN and lamina propria from B27-Tg rats. Finally, we observed that after TLR-7 stimulation, the migration of XCR1+ cDCs to MLN was proportionally reduced in B27-Tg rats. Our results demonstrate for the first time a decreased proportion of tolerogenic XCR1+ cDCs subpopulation in SpA target organs in the B27-Tg rats, which may affect the maintenance of self-tolerance and control inflammation
Moltó, Revilla Anna. "Management of early spondyloarthritis: from diagnosis to treatment in clinical practice". Doctoral thesis, Universitat Autònoma de Barcelona, 2015. http://hdl.handle.net/10803/295711.
Pełny tekst źródłaThe objective of this research was to evaluate diagnosis and treatment of early axial spondyloarthritis in clinical practice. For this, we have included in this thesis three articles that reflect the three milestones of our research. First, we aimed to validate the ASAS criteria for axial spondyloarthritis in a clinical practice setting, by evaluating their performance both in terms of classification but also of diagnostic purposes, compared to other sets of criteria and in different spondyloarthritis presentations (e.g. psoriatic arthritis, IBD related-arthritis, etc..). Secondly, since the “clinical” arm of the ASAS criteria for axial spondyloarthritis is not well recognized by many in the medical community, we aimed to compare the demographics, phenotypic and disease characteristics of patients fulfilling the “imaging” and “clinical” arm of the ASAS. Finally, we aimed to evaluate the treatment effect of TNF-alpha blockers in clinical practices and the potential predictors of response (e.g. the fulfilment of the ASAS criteria for axial spondyloarthritis).
Song, In-Ho [Verfasser]. "Frühe Diagnose, Monitoring und Therapie der axialen Spondyloarthritis / In-Ho Song". Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2012. http://d-nb.info/102849730X/34.
Pełny tekst źródłaAita, Ada. "Genetics in TNF-TNFR pathway: a complex network causing spondyloarthritis and conditioning response to therapy". Doctoral thesis, Università degli studi di Padova, 2017. http://hdl.handle.net/11577/3425710.
Pełny tekst źródłaIntroduzione. Le spondiloartriti sieronegative (SpA) sono un gruppo di malattie infiammatorie croniche risultanti da una complessa interazione tra fattori genetici (tra cui, HLA-B27 è il maggior predisponente) e ambientali. Ed è tale interazione ad indurre l'attivazione di processi autoinfiammatori e la disregolazione del sistema immunitario caratterizzanti la malattia. In molti casi, una diagnosi precoce ed un adeguato monitoraggio dell’ attività di malattia risultano difficili a causa della sovrapposizione delle caratteristiche cliniche tra le diverse forme. Il ritardo nella diagnosi e conseguentemente nel trattamento, è inoltre dovuto al fatto che, gli indici d’infiammazione comunemente utilizzati nella pratica clinica, la velocità di eritrosedimentazione (VES) ed la proteina C-reattiva (PCR), sono nella norma in almeno metà dei pazienti con chiara espressione dell’attività di malattia. Il ritardo nella diagnosi conferisce a questi pazienti un carico sintomatico importante ed una perdita di funzione durante gli anni di vita produttiva. Pertanto, forte attenzione è attualmente rivolta all’identificazione di marcatori biochimici e genetici utili alla diagnosi e di fattori prognostici necessari a valutare l'efficacia del trattamento. Tra i fattori genetici predisponenti, è noto il ruolo di HLA-B27, che contribuisce però solo per il 20-30% all'ereditarietà totale, mentre il complesso maggiore di istocompatibilità (MHC) rappresenta circa il 40-50% del rischio genetico di sviluppare la patologia. Questo dato ha suggerito il probabile coinvolgimento di altri geni nel meccanismo patogenetico. Studi di associazione genetica hanno permesso di identificare un certo numero di altri geni, associati alla patologia, sia nel locus MHC che in altri loci. In questo contesto, di grande interesse è lo studio della genetica di TNF-α, considerato il ruolo di tale citochina nel propagare e perdurare dell'infiammazione. Sebbene numerosi studi abbiano dimostrato l’associazione tra i polimorfismi di geni coinvolti nella via del segnale del TNF-α (es. TNFA, TNFSF15, TNFR1 e TRADD) e la patologia di SpA, i risultati sono discordanti. Di grande interesse sono anche le varianti del MEFV gene, coinvolto nella patogenesi della malattia autoinfiammatoria Febbre Mediterranea Familiare (FMF). Studi recenti hanno, infatti, dimostrato che le SpA, ed in particolare la spondilite anchilosante (AS), sono molto comuni tra i pazienti affetti da FMF e che questi pazienti possono presentarsi con AS come unica manifestazione. Questo studio, condotto su 91 pazienti e 223 controlli, provenienti da una regione italiana del Nord-Est, si propone di identificare fattori bioumorali (biochimici ed ematologici) e genetici al fine di supportare i processi diagnostici e prognostici (risposta alla terapia). In particolare, oltre ai parametri biochimici ed ematologici, è stato valutato se polimorfismi nella regione del promotore del gene TNFA, o dei geni TNFRSF1A e MEFV, possano concorrere con l’allele HLA-B27 all’aumento del rischio di sviluppare la malattia e/o nel predire la risposta agli inibitori del TNF-α. Metodi. La popolazione studiata comprendeva 91 pazienti con diagnosi di SpA (età media ± deviazione standard: 52.1 ± 12.5 anni; 57 maschi, 34 femmine) e 223 donatori di sangue (età media ± deviazione standard: 46 ± 11 anni; 146 maschi, 77 femmine) provenienti dalla Regione Veneto, una regione italiana del Nord-Est. Tra i pazienti, 36 presentavano AS e 55 artrite psoriasica (PsA), con diagnosi formulata sulla base dei criteri rispettivamente di New York e CASPAR. Il protocollo di questo studio è stato approvato dal Comitato Etico Istituzionale locale dell’Università-Azienda Ospedaliera di Padova, Italia (Prot.n. 3024P / 13), e tutti i soggetti arruolati hanno firmato un consenso informato prima di partecipare allo studio. Per ciascun soggetto arruolato, sono stati raccolti i dati demografici e fisiologici, la storia clinica e familiare. Sono stati raccolti poi, campioni di sangue, al fine di valutare l’emocromo e la VES, e di determinare i livelli di PCR, acido urico, prealbumina, alanina aminotransferasi (ALT) e glucosio. L’analisi molecolare dei geni MEFV (esoni 2,3,5 e 10) e TNFRSF1A (esoni 2,3,4 e 6) è avvenuta mediante sequenziamento diretto. La determinazione degli alleli HLA-B27 e dei polimorfismi del gene TNFA (-1031T>C;-857C>T;-376G>A;-308G>A;-238G>A) è stata condotta mediante PCR in Real-Time. La determinazione degli alleli HLA-CW6 è avvenuta mediante un test genetico molecolare CE-IVD, disponibile in commercio, che adotta la tecnologia microarray. L’analisi statistica è stata effettuata utilizzando il software STATA (versione 13.1). Risultati. Un maggior numero di cellule polimorfonucleate circolanti e livelli di PCR più elevati sono stati rilevati nei pazienti affetti da SpA rispetto ai controlli. Inoltre, i pazienti affetti da PsA hanno mostrato livelli più elevati di ALT, non solo rispetto ai controlli, ma anche rispetto a pazienti affetti da AS. In ogni caso tali indici non erano molto elevati e spesso risultavano compresi entro gli intervalli di riferimento. Come atteso, gli alleli HLA-B27 sono risultati associati all’AS (χ2=120.1; p<0.0001). Sebbene una frequenza leggermente maggiore degli alleli HLA-CW6 sia stata osservata tra i pazienti con AS (circa il 6%) o PsA (circa il 13%) rispetto ai controlli (circa 4%), la differenza non è risultata essere statisticamente significativa. Nessuno dei polimorfismi del gene TNFA è risultato singolarmente associato alla diagnosi SpA, né a quella di AS o PsA, se valutate indipendentemente. Sono stati, poi, statisticamente dedotti gli aplotipi derivanti dalle coppie di combinazioni dei cinque polimorfismi studiati. Gli aplotipi più frequenti nei controlli sono stati selezionati come aplotipi di riferimento, e solo l’aplotipo -1031C/-308G è risultato significativamente associato con l’AS (p=0.015) esercitando in questa malattia un ruolo protettivo (odds ratio: 0.43; intervallo di confidenza al 95%: 0.22- 0.85). Tre polimorfismi sono stati identificati nel gene TNFRSF1A e tra questi, solo i polimorfismi R92Q (Frequenza dell’allele minore- MAF = 0.034) e c.625 + 10A> G (MAF = 0.479) sono stati selezionati a causa del potenziale ruolo funzionale. Entrambi i polimorfismi non sono risultati associati con la diagnosi di SpA (χ2 = 1.073 e p = 0.300 per R92Q; χ2 = 4.721 e p = 0.094 per c.625 + 10A> G). Il polimorfismo c.625 + 10A> G è però, risultato essere associato con la risposta alla terapia con anti-TNF, valutato sulla base di un punteggio BASDAI inferiore / uguale o superiore a 4, a 10 mesi dall’inizio della terapia (p = 0.031). Ventuno polimorfismi sono stati identificati nel gene MEFV e tra questi, 10 noti per il potenziale significato funzionale. Tali varianti alleliche sono risultate estremamente rare nella nostra popolazione (MAF <0.025) ad eccezione di R202Q (MAF = 0.27). Nessun polimorfismo è risultato essere associato con la diagnosi SpA (p> 0.05). Conclusioni. In conclusione, i risultati di questo studio suggeriscono il ruolo rilevante della genetica della via del segnale TNF-TNFR nel complesso sistema che induce la patogenesi di SpA e condiziona la risposta alla terapia. Il gene TNFA, nella popolazione oggetto di studio, si è dimostrato un fattore predisponente per lo sviluppo di SpA, ma soprattutto di AS. Al contrario, la genetica del gene MEFV non sembra mostrare alcun impatto in questo gruppo di malattie. L'aplotipo TNFA-1031C/-308G, potenzialmente associato alla produzione di livelli più bassi di TNF-α, sembra esercitare un ruolo protettivo nella patogenesi di AS, mentre è emerso che il polimorfismo c.625 TNFRSF1A + 10A> G costituisce un potenziale fattore predittivo di risposta alla terapia con anti-TNFα.
Poddubnyy, Denis [Verfasser]. "Prediction and prevention of disease progression in early axial spondyloarthritis / Denis Poddubnyy". Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2014. http://d-nb.info/1047336804/34.
Pełny tekst źródłaMoz, Stefania. "Emerging role of monocytes and of their intracellular calcium content in spondyloarthritis". Doctoral thesis, Università degli studi di Padova, 2018. http://hdl.handle.net/11577/3425393.
Pełny tekst źródłaIntroduzione. Le Spondiloartriti (SpA) sono un gruppo di malattie multifattoriali caratterizzate da una complessa interazione tra fattori genetici ed ambientali che determinano una disregolazione del sistema immunitario e l’attivazione di processi infiammatori a livello articolare, in particolar modo nelle articolazioni sacro-iliache. A differenza dell’artrite reumatoide, nelle SpA non esistono dei biomarcatori specifici di attività di malattia che vengono utilizzati nella pratica clinica. Pertanto, la ricerca di nuovi biomarcatori potrebbe essere d’ausilio per una diagnosi precoce e per un adeguato monitoraggio dell’attività di malattia, oltre che essere impiegati come fattori prognostici, misure di outcome e strumenti di valutazione dell’efficacia di trattamento.Nei pazienti con SpA, i macrofagi che infiltrano le articolazioni e che derivano principalmente dai monociti circolanti non esprimono solo citochine infiammatorie come TNF-α, IL-1β o TGF-β ma anche enzimi coinvolti nel rimodellamento tissutale come le metallo proteinasi di matrice (MMPs). La metalloproteinasi di matrice 3 (MMP-3), infatti, è riconosciuta come una molecola altamente espressa nel tessuto sinoviale e nel sangue periferico dei pazienti con SpA. Studi recenti hanno evidenziato che le metallo proteinasi di matrice 8 e 9 (MMP8 e MMP9) vengono prodotte dalle cellule mononucleate derivate da sangue periferico (PBMCs) quando vengono stimolate da calprotectina (eterodimero formato dalle proteine S100A8 e S100A9).Vi è poi una crescente evidenza del ruolo patogenetico nelle Spa svolto dalle cellule appartenenti all’immunità innata quali macrofagi, mastociti e neutrofili; il tessuto sinoviale dei pazienti con SpA infatti è caratterizzato da una elevata vascolarizzazione e quindi da una forte infiltrazione delle cellule immunitarie. In queste cellule i segnali di calcio intracellulare sono essenziali nella regolazione di numerose funzioni cellulari incluse proliferazione, differenziazione, apoptosi e trascrizione genica. Lo scopo di questo lavoro è stato quello di analizzare i livelli di espressione genica delle molecole TNF-α, IL-1β, TGF-β, S100A8, S100A9, MMP3, MMP8 e MMP9 e di valutare se le variazione dei flussi di calcio intracellulare ([Ca2+]i) nei PBMCs potrebbero essere associati alla presenza di SpA. Metodi.La popolazione studiata comprendeva 64 pazienti con diagnosi di SpA (età media ± deviazione standard: 39.5 ± 13.2 anni; 39 maschi, 25 femmine) e 100 controlli sani (età media ± deviazione standard: 46.6 ± 8.5 anni; 58 maschi, 42 femmine). Tra i pazienti, 26 (40.6%) presentavano spondilite anchilosante (AS) e 38 (59.3%) artrite psoriasica (PsA), con diagnosi formulata sulla base dei criteri rispettivamente di New York e CASPAR. Per ciascun soggetto arruolato, sono stati raccolti i dati demografici e fisiologici, la storia clinica e familiare. Sono stati raccolti poi, campioni di sangue, al fine di valutare l’emocromo e la VES, e di determinare i livelli di PCR, acido urico, prealbumina, alanina aminotransferasi (ALT) e glucosio. Per ciascun soggetto è stata effettuata un’analisi di espressione genica relativa (Real Time PCR) di TNF-α, IL-1β, TGF-β, S100A8, S100A9, MMP3, MMP8 e MMP9. La determinazione dei flussi di calico intracellulare ([Ca2+]i) nei pazienti e nei controlli è stata effettuate mediante microscopio ad epifluorescenza. Risultati. I livelli di espressione genica relativa nei PBMCs delle citochine infiammatorie of TNF-α, IL-1β, TGF-β erano simili nei pazienti con AS e PsA se comparati ai livelli di espressione nei controlli sani. Le variazioni dei livelli di espressione di TNF-α, TGF-β e IL-1β correlavano tra di loro. I livelli di espressione di TNF-α però risultavano correlati in maniera diretta, nei pazienti, con la presenza di una familiarità per la malattia (t=-2.5386, p=0.013). I livelli di espressione di MMP8 e MMP9 non risultavano essere associati con la diagnosi di SpA e non correlavano con gli indici clinici di attività di malattia.Anche i livelli di espressione di S100A9 non risultavano essere associati con la diagnosi di SpA mentre i livelli di espressione di S100A8 (F=3.29, p=0.039) erano ridotti nei pazienti con PsA.I livelli di espressione di S100A8 e S100A9 correlavano in maniera significativa con il numero di cellule infiammatorie circolanti e S100A8 correlava con i valori di PCR e VES. Dall’analisi dei dati ottenuti dai controlli sani e dai pazienti risultava evidente come la maggior parte dei monociti dei soggetti di controllo presentassero pulsazioni regolari di calcio intracellulare a differenza delle cellule ottenute da pazienti.I pazienti affetti da AS presentavano una ridotta percentuale di monociti con oscillazioni dei flussi di calcio intracellulare rispetto ai controlli sani (F=6.15, p=0.003). La percentuale di monociti con variazione di calcio intracellulare e l’ espressione delle molecole studiate non risultavano essere correlati ne con il tipo di terapia ne con il tipo di farmaco utilizzato. Conclusioni. In conclusione, I risultati di questo studio hanno evidenziato che nei pazienti con SpA vi è una ridotta espressione della proteina legante calcio S100A8 e vi è un decremento dei flussi di calcio intracellulare rispetto ai controlli sani, suggerendo che la presenza della malattia influenza i meccanismi "on-off" che regolano la concentrazione di calcio intracellulare.
Althoff, Christian [Verfasser]. "Ganzkörper-MRT und interventionell-radiologische Therapie von Patienten mit Spondyloarthritis / Christian Ernst Althoff". Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2017. http://nbn-resolving.de/urn:nbn:de:kobv:188-fudissthesis000000105806-5.
Pełny tekst źródłaAlthoff, Christian Ernst [Verfasser]. "Ganzkörper-MRT und interventionell-radiologische Therapie von Patienten mit Spondyloarthritis / Christian Ernst Althoff". Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2017. http://d-nb.info/1143596080/34.
Pełny tekst źródłaRysnik, Oliwia Julita. "The expression patterns of non-classical and classical forms of HLA-B27 in spondyloarthritis". Thesis, University of Oxford, 2015. https://ora.ox.ac.uk/objects/uuid:7d902d4e-6b9c-4c8c-9f88-5de4d7c7a154.
Pełny tekst źródłaTsyplenkova, Olga [Verfasser], Jürgen [Gutachter] Braun i Roland [Gutachter] Willburger. "Prävalenz extraspinaler Manifestationen bei Patienten mit Spondyloarthritis / Olga Tsyplenkova ; Gutachter: Jürgen Braun, Roland Willburger". Bochum : Ruhr-Universität Bochum, 2017. http://d-nb.info/1144614589/34.
Pełny tekst źródłaButscher, Annemarie [Verfasser], i Jörg [Akademischer Betreuer] Henes. "Prävalenz der Spondyloarthritis bei Patienten mit chronisch-entzündlichen Darmerkrankungen / Annemarie Butscher ; Betreuer: Jörg Henes". Tübingen : Universitätsbibliothek Tübingen, 2019. http://d-nb.info/1204879907/34.
Pełny tekst źródłaHarvard, Stephanie. "Economic evaluations in the context of treatment recommendations in spondyloarthritis : analyses from the DESIR cohort". Thesis, University of British Columbia, 2017. http://hdl.handle.net/2429/63323.
Pełny tekst źródłaMedicine, Faculty of
Population and Public Health (SPPH), School of
Graduate
Amtenbrink, Anna Luise [Verfasser]. "Eignet sich die Sonographie der Ferse als Screeningparameter zur Diagnosestellung einer Spondyloarthritis? / Anna Luise Amtenbrink". Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2013. http://d-nb.info/1035406322/34.
Pełny tekst źródłaConrad, Kristina. "Quantifizierung löslicher und zellulärer Biomarker bei Patienten mit Spondyloarthritiden". Doctoral thesis, Humboldt-Universität zu Berlin, Lebenswissenschaftliche Fakultät, 2015. http://dx.doi.org/10.18452/17332.
Pełny tekst źródłaAxial Spondyloarthitis (axSpA) is a chronic inflammatory-rheumatic disease of unknown cause. It is characterized by inflammations of the sacroiliac joints (SIG) and the spinal joints. In addition an ankylosis in the SIG can develop in the progression of the disease as well as syndesmophytes at the vertebral body. Since the majority of axSpA-patients also have sub-clinical mucosal inflammations, mucosal anti-gens are discussed as triggers of the inflammation. For the diagnosis and prognosis of axSpA there are only a few serological markers with high sensitivity and specificity until now. In this thesis it could be shown that the serum concentration of CTX-II, BMP-2 and LBP exhibit a high diagnostic potential for axSpA, while the serum concentration of BMP-2, PINP and VEGF could be suitable markers for the forecast of radiographic progression. Furthermore increased LPS-, LBP- and IL-6-serum concentrations could be verified, which can be an indicator for the translocation of bacterial antigenes. The monocyte characterization showed increased frequencies of the pro-inflammatory CD14++CD16- sub population and a reduced portion of CD14++CD16+ monocytes in patients with axSpA. Functionally the monocytes of axSpA-patients showed an in vivo pre-activation with increased spontaneous and by suboptimal bacterial stimuli induced release of pro-inflammatory cytokines with simultaneously reduced reactivity towards LPS in vitro. This pre-activation could be detected for patients undergoing standard therapy, but not for those under TNF-blocker-therapy. Interestingly for the standard therapy patients there was a connection between the activity of the disease, meaning the BASDAI, and the frequency of the cytokine-producing monocytes. Therefore biomarkers with diagnostic and prognostic relevance could be identified in line with this thesis. The significance of these biomarkers has to be researched further in independent cohorts.
Weineck, Henning [Verfasser]. "Epidemiologische, klinische, laborchemische und bildgebende Differenzierung der Osteitis condensans ilii und der axialen Spondyloarthritis / Henning Weineck". Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2020. http://d-nb.info/1206184388/34.
Pełny tekst źródłaArévalo, Salaet Marta. "El papel del HLA-B27 en la Espondiloartritis Axial". Doctoral thesis, Universitat Autònoma de Barcelona, 2021. http://hdl.handle.net/10803/671576.
Pełny tekst źródłaEn la tesis que presento se evalúan las implicaciones de la presencia del HLA-B27 en el fenotipo y las comorbilidades de pacientes con Espondiloartritis Axial
The present thesis assesses the implications of the presence of HLA-B27 in phenotype and comorbidities in Axial Spondyloarthritis patients
Menegatti, Silvia. "Anti-TNF therapy in axial spondyloarthritis : mechanism of action and prediction of therapeutic responses using immunological signatures". Thesis, Sorbonne Paris Cité, 2017. http://www.theses.fr/2017USPCC128.
Pełny tekst źródłaThe introduction of anti-TNF therapy has proven effective to reduce inflammation and clinical symptoms in several chronic inflammatory diseases. However, 30-40% of patients do not respond to TNF blockers and it is currently not possible to predict responsiveness of patients to anti-TNF therapy. Furthermore, their impact on the immune system is incompletely understood. The goals of my PhD project were (i) to define the impact of anti-TNF therapy on immune responses to microbial challenges and stimuli targeting specific immune pathways in spondyloarthritis (SpA) patients, and (ii) to identify immunological correlates associated with therapeutic responses to TNF-blockers.Using a set of whole-blood, syringe-based assays to perform ex vivo stimulation while preserving physiological cellular interactions (TruCulture assays), we have performed a pilot study in SpA patients and investigated immune responses to 20 different stimuli before and 3 months after initiation of anti-TNF therapy. These findings were validated in a replication cohort, also assessing the effects of anti-TNF agents after only one week of treatment. We observed a highly significant reduction of the secretion of IL-1ra, IL-1β, IL-8 and MIP-1β in response to selected stimuli after 3 months of treatment compared to the baseline. Interestingly, these changes were already detectable after a single injection of an anti-TNF agent. To gain insight into the molecular mechanism of TNF blockers, we profiled gene expression in the stimulation cultures from all patients. Quantitative set analysis for gene expression (QuSAGE) revealed that the gene modules most affected by anti-TNF therapy are NF-kB transcription factors and inhibitors and NF-kB target genes, including TNF itself and IL1B. Our data suggest that TNF-blockers primarily act by disrupting an autoregulatory loop driven by NF-kB. We also tested whether there is a correlation between the responses of immune cells to specific stimuli and the clinical response to TNF-blockers. The decision tree model that we trained and validated suggests that SpA patients who expressed lower levels of PAX5 and higher levels of SPP1 in response to SEB stimulation before initiation of anti-TNF therapy had the best therapeutic responses. Our study shows that TruCulture assays are an efficient and robust tool to monitor immune functions in SpA patients and that the effects of anti-TNF therapy can be measured when immune cells are challenged, but not at steady state. Our data also indicate that analyzing immune responses in patients before therapy is a promising strategy to develop biomarkers for prediction of therapeutic responses to TNF-blockers
Vahldiek, Janis Lucas [Verfasser]. "Frühdiagnose der axialen Spondyloarthritis : Validierung eines neuen Screening-Verfahrens bei Patienten mit chronischem Rückenschmerz / Janis Lucas Vahldiek". Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2011. http://d-nb.info/1025510720/34.
Pełny tekst źródłaJouhault, Quentin. "Modulation de la balance Th17/Treg par l’IL-27 et ICOS dans un modèle animal de Spondyloarthrite". Thesis, Université Paris-Saclay (ComUE), 2017. http://www.theses.fr/2017SACLV008/document.
Pełny tekst źródłaSpondyloarthritis (SpA) is a frequent chronic rheumatic inflammatory disorder with a prevalence of 0.43% in France and closely associated to HLA-B27. To date, there is no curative treatment and pathophysiological mechanisms involved in this pathology remain elusive. To better understand these mechanisms, we studied two crucial cell populations, dendritic cells (DC) and CD4+ T cells in rats transgenic for HLA-B27 and human β2 microglobulin (B27 rats) which spontaneously develop a phenotype closely resembling human spndyloarthritis. Previous studies demonstrated that accumulation of pathogenic IL-17 producing T cells (Th17 cells) and several function defects of DCs are correlated with SpA development in B27 rats.First, we focused on regulatory T cells, whose role is to prevent the establishment of pathogenic immune responses. We discovered that Treg from B27 rats have a pro-inflammatory phenotype. They overexpress IL-17 and underexpress anti-inflammatory IL-10, linked to ICOS overexpression. Furthermore, B27 rats knock-out for ICOS (B27 ICOS KO rats) have reduced severity of clinical symptoms compared to B27 ICOS WT rats. This protective effect is correlated with a reduced proportion of Th17 cells. These results highlight the crucial role of ICOS in rat SpA physiopathology.In the second part of this work we studied the consequences of IL-27 underexpression by B27 DC, a cytokine known to inhibit Th17 development. Addition of exogenous IL-27 reduces IL-17 and increases IL-10 productions by differentiated T cells (Teff and Treg) and by naive T cells polarized in vitro. Interestingly, IL-27 also reduces IL-17 production by circulating CD4+ T cells isolated from blood of SpA patients.This work demonstrate for the first time the key role of IL-27 and ICOS in the control of inflammation in B27 rats and highly suggest that these molecules may be new promising therapeutic targets in SpA
Avram, Annalina [Verfasser], Timm Henning [Akademischer Betreuer] Westhoff i Roland Ernst [Akademischer Betreuer] Willburger. "Früherkennung von Patienten mit axialer Spondyloarthritis in der Primärversorgung / Annalina Avram. Gutachter: Timm Henning Westhoff ; Roland Ernst Willburger". Bochum : Ruhr-Universität Bochum, 2016. http://d-nb.info/1095884387/34.
Pełny tekst źródłaAvram, Annalina Verfasser], Timm Henning [Akademischer Betreuer] Westhoff i Roland Ernst [Akademischer Betreuer] [Willburger. "Früherkennung von Patienten mit axialer Spondyloarthritis in der Primärversorgung / Annalina Avram. Gutachter: Timm Henning Westhoff ; Roland Ernst Willburger". Bochum : Ruhr-Universität Bochum, 2016. http://d-nb.info/1095884387/34.
Pełny tekst źródłaZurrin, Daniela Elisabeth [Verfasser], i Torsten [Akademischer Betreuer] Witte. "Die Rolle von CD74 Autoantikörpern bei der Spondyloarthritis / Daniela Elisabeth Zurrin ; Akademischer Betreuer: Torsten Witte ; Klinik für Immunologie und Rheumatologie". Hannover : Bibliothek der Medizinischen Hochschule Hannover, 2019. http://d-nb.info/1201832748/34.
Pełny tekst źródłaSieber, Isabella [Verfasser], Jürgen [Gutachter] Braun i Ralf-Hermann [Gutachter] Wittenberg. "Beteiligung peripherer Strukturen bei Patienten mit axialer oder peripherer Spondyloarthritis / Isabella Sieber ; Gutachter: Jürgen Braun, Ralf-Hermann Wittenberg ; Medizinische Fakultät". Bochum : Ruhr-Universität Bochum, 2021. http://d-nb.info/1230631232/34.
Pełny tekst źródłaHilgert, Elke [Verfasser]. "Vergleich von klinischer Krankheitsaktivität und objektivem Nachweis akut entzündlicher Veränderungen in der Magnetresonanztomographie bei Patienten mit axialer Spondyloarthritis / Elke Hilgert". Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2008. http://d-nb.info/1027497608/34.
Pełny tekst źródłaCostantino, Félicie. "Recherche de nouveaux facteurs génétiques de susceptibilité à la spondyloarthrite grâce à une approche associant études familiales et génomique fonctionnelle". Thesis, Paris 5, 2014. http://www.theses.fr/2014PA05T056/document.
Pełny tekst źródłaSpondyloarthritis (SpA) is a frequent and disabling chronic rheumatic disease. To date, more than 20 susceptibility loci have been identified, including HLA-B27 in the major histocompatibility complex (MHC). Most of the disease heritability remains to be elucidated. The aim of the study was to identify new genetic factors of susceptibility to SpA using an approach combining genetics and functional genomics. In the first part of this work, we genotyped SpA multiplex families with microarrays of 250,000 SNPs. Non parametric linkage analysis revealed a new locus significantly linked to SpA outside the MHC, in 13q13. Further studies on this locus allowed us to map the disease interval to a 1.3 Mb region, which will be soon sequenced. Moreover, family-based association study identified a significant association between one intronic SNP in MAPK14 and SpA. We also showed that one of the known ankylosing spondylitis-associated SNP in IL23R was indeed associated with sacroiliitis in SpA. We have also compared dendritic cells gene expression between nine SpA patients and ten controls and identified 81 genes differentially expressed. Moreover, we showed that ERAP1 gene expression (and at a less extent protein expression and enzymatic activity) is under the control of several polymorphisms in the gene which has previously been associated with SpA
Neumann, Anna-Dorothea [Verfasser], Hans Jürgen [Akademischer Betreuer] Rech i Georg [Gutachter] Schett. "Cortical bone loss is an early feature of nonradiographic axial spondyloarthritis / Anna-Dorothea Neumann ; Gutachter: Georg Schett ; Betreuer: Hans Jürgen Rech". Erlangen : Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 2021. http://d-nb.info/1241332673/34.
Pełny tekst źródłaWhyte, Jessica. "Investigating the mechanisms of ankylosing spondylitis-associated genetic variants". Thesis, Queensland University of Technology, 2021. https://eprints.qut.edu.au/211291/1/Jessica_Whyte_Thesis.pdf.
Pełny tekst źródłaAhomaa, Eerik Johannes [Verfasser], Uta [Gutachter] Kiltz i Klaus [Gutachter] Schmidt. "Zusammenhang zwischen selbstberichteter Funktionsfähigkeit und tatsächlicher Leistungsfähigkeit bei Patienten mit axialer Spondyloarthritis / Eerik Johannes Ahomaa ; Gutachter: Uta Kiltz, Klaus Schmidt ; Medizinische Fakultät". Bochum : Ruhr-Universität Bochum, 2021. http://d-nb.info/1236813782/34.
Pełny tekst źródłaVigneswaran, Mathura [Verfasser], Jürgen [Gutachter] Braun i Roland Ernst [Gutachter] Willburger. "Wirksamkeit einer Behandlung mit Nicht-steroidalen Antirheumatika bei Patienten mit axialer Spondyloarthritis / Mathura Vigneswaran ; Gutachter: Jürgen Braun, Roland Ernst Willburger ; Medizinische Fakultät". Bochum : Ruhr-Universität Bochum, 2020. http://d-nb.info/121785987X/34.
Pełny tekst źródłaAngeli, Ricardo dos Santos. "Estudo comparativo de duas técnicas laboratoriais para a detecção do HLA-B27 em pacientes portadores de espondiloartrite axial". reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2017. http://hdl.handle.net/10183/182072.
Pełny tekst źródłaIntroduction: Axial spondyloarthritis (SpA-ax) is an inflammatory and chronic disease of the Spondyloarthritis (SpA) group. It affects the skeletal muscle system causing inflammation of the axial joints (especially of the sacroiliac). When these manifestations are evidenced by imaging tests, a characterization of Ankylosing Spondylitis (AS). Otherwise, we call the non-radiographic SpA-axial (SpA-ax-nr). AS marked by the inflammatory involvement of the axial and appendicular skeletal joints. The diagnosis is based on clinical and radiological findings, as well as the on the elevation of inflammatory markers and presence of HLA-B27. There are several methodologies to identify the HLA-B27 gene and a Polymerase Chain Reaction (PCR) is considered the reference method. However, its use on a large scale does not progress because it takes into account the cost, offer of the exam and the running time to obtain the result. In this context, Flow Cytometry (FC) emerges as an alternative method, helping with the physician in the determination of this genetic marker, important for the diagnosis and prognosis of disease. Objective: To evaluate the correlation between FC and PCR, comparing sensitivity and specificity for detection of HLA-B27 in patients with established diagnosis of SpA-ax. Methods: A cross sectional study including 62 patients recruited during 2015 month was conducted in Hospital de Clínicas de Porto Alegre, an university public hospital. The sample, recruited by convenience in the SpA clinic, was composed of patients ≥ 18 years old, fulfilling the Assessment of Spondyloarthritis (ASAS) criteria SpA-ax. All participants underwent HLA-B27 typing through FC and PCR. The kappa statistic was used to calculate the concordance between the FC and PCR. Taking PCR as the gold standard, sensitivity and specificity of FC to detect HLA-B27 were calculated. Results: The Kappa coefficient obtained to determine the agreement between the tests was 0.454. Sixty two patients were included in the study, sixty met the criteria for diagnosis of AS and two for SpA-ax-nr, 64.5% of the patients were male, 88.7% were self-declared mean age (± standard deviation) was 54.5 ± 12 years and median time (25th and 75th percentiles) for diagnosis was 14 (9 and 24) years. Among the clinical characteristics presented by the population studied, there was a statistically significant difference for peripheral arthritis, wich was more frequent in the HLA-B27 negative group than in the HLA-B27 positive group (P = 0.032). In the correlation analysis, 90.3% presented HLA-B27 positive typing by FC and 79.0% by PCR technique. When PCR was considered the gold standard, CF had a sensitivity of 98.0%, specificity of 38.5% and an accuracy of 85.5%. Conclusion: Despite the low specificity presented by FC, our study demonstrated that FC has high sensitivity and good accuracy, which makes it a good alternative to be used as a screening test in the search for the characterization of the disease. Despite the moderate agreement with the reference technique, FC could help the physician to exclude falsely negative results, thus rationalizing laboratory investigation for the diagnosis of AS.
Matkowska-Jaron, Aneta [Verfasser], Jürgen [Gutachter] Braun i Heiner [Gutachter] Appel. "Der Verlauf von Patienten mit undifferenzierter Spondyloarthritis und ankylosierender Spondylitis : ein klinischer Vergleich / Aneta Matkowska-Jaron ; Gutachter: Jürgen Braun, Heiner Appel ; Medizinische Fakultät". Bochum : Ruhr-Universität Bochum, 2019. http://d-nb.info/1177363976/34.
Pełny tekst źródłaLorenzin, Mariagrazia. "Spine and sacroiliac joints on nuclear magnetic resonance imaging and research of serological biomarkers predictive of severity and disease activity in early axial spondyloarthritis". Doctoral thesis, Università degli studi di Padova, 2018. http://hdl.handle.net/11577/3424857.
Pełny tekst źródłaRecenti studi si sono concentrati sull’impiego della risonanza magnetica (RMN) e di nuovi biomarcatori che potrebbe facilitare la diagnosi precoce della spondiloartrite assiale (axSpA) e identificare gli individui a più alto rischio di sviluppare la malattia. Scopo del lavoro:Valutare:1)biomarcatori potenzialmente utili per la diagnosi precoce di axSpA e le loro correlazioni con gli indici di attività di malattia e di imaging;2)la prevalenza delle lesioni alla RMN del rachide e del bacino in pazienti (pts) con lombalgia (LBP);3)la correlazione tra la sede del dolore assiale e la localizzazione delle lesioni alla RMN.Materiali e Metodi:Settantadue pts con LBP (≥3 mesi,≤2 anni, insorgenza≤45 anni) sono stati valutati con:esame obiettivo, questionari, indagini sierologiche, radiografie e risonanza magnetica del rachide e delle articolazioni sacro-iliache (SI) al basale e durante un periodo di follow-up di 24 mesi.Due reumatologi esperti hanno formulato la diagnosi axSpA secondo i criteri ASAS “SpondyloArthritis International Society” per axSpA.Sono stati valutati i seguenti indici:Bath Ankylosing Spondylitis Metrology Index (BASMI);Maastricht Ankylosing enthesitis Spondilities Score (MASES);Bath Ankylosing Spondylitis Disease Activity Index (BASDAI);Bath Ankylosing Spondylitis Functional Index (BASFI);Ankylosing Spondylitis disease activity score (ASDAS);Visual Analogue Scale (VAS pain);VAS night pain;VAS disease activity;Bath Ankylosing Spondylitis Patient Global Score (BASG1);BASG2;Health Assessment Questionnaire (HAQ);VES;PCR ultrasensibile (hs-PCR);la metallo-proteinasi 3 (MMP3);interleuchine (IL) IL-22, IL-17, IL-23.Le immagini alla radiografia e alla RMN sono state valutate in modo indipendente da 2 radiologi secondo i criteri SPARCC, mSASSS e mNY.La sede del dolore assiale e delle lesioni alla RMN sono state classificate in 4 siti: colonna cervicale/toracica/lombare e regione glutea.L'associazione tra la sede del dolore e delle lesioni alla RMN è stata valutata tramite Odds Ratio (OR).I test Spearman e Kruskal Wallis sono stati usati per confrontare tutti gli indici di queste coorti.Risultati: I pts sono stati diagnosticati come axSpA e classificati secondo i criteri ASAS come: 1)21 pts classificati axSpA secondo il braccio dell’imaging; 2)29 pts classificati axSpA secondo il braccio clinico; 3)25 pts che non soddisfacevano i criteri ASAS.L'età media di insorgenza della LBP era 28,51 anni, il 45,3% era di sesso maschile,l'HLA-B27 era positivo nel 38,7%.Il 56% dei pts mostrava segni di edema midollare osseo (BME) a carico della RMN del rachide e il 61,3% a carico della RMN delle SI.Diciotto pts (24%) presentavano una RMN delle SI negativa per BME con una RMN del rachide positiva.L’OR tra la sede del dolore e delle lesioni BME era rispettivamente:20.78(p=NS); 163.93(p=0.0006); 0,34(p=NS)per la colonna cervicale/toracica/lombare e 304,88 (p=0,0203) per la regione glutea.È stata anche trovata una correlazione significativa tra dolore toracico/entesite del distretto toracico (OR=32.69; p=0.0336). C'era una differenza significativa tra le tre coorti per quanto riguarda la prevalenza di sacroileite radiografica, sacroileite attiva alla RMN e punteggio SPARCC-SI. È stata trovata una correlazione tra IL-22 e alcuni indici clinici.La correlazione tra mSASSS, MMP3 e hsPCR è stata una scoperta interessante.Conclusioni:Il sito del dolore si correla significativamente con le lesioni BME nei distretti toracico e gluteo. Dato che sono state osservate immagini positive alla RMN del rachide in assenza di sacroileite, riteniamo che lo studio del rachide possa avere un valore aggiunto nella diagnosi di early axSpA.I valori di IL-22, MMP3 e hsPCR correlano con alcuni indici di attività della malattia e con mSASSS.Sono necessari studi osservazionali più ampi per confermare questi risultati preliminari.
Toledo, Ricardo Acayaba de. "Sinais clínicos em pacientes com espondiloartrites na presença e na ausência do gene HLA-B*27". Faculdade de Medicina de São José do Rio Preto, 2013. http://bdtd.famerp.br/handle/tede/183.
Pełny tekst źródłaIntroduction: Spondyloarthritis is a group of diseases with clinical, laboratory and image similar. Analysis of clinical manifestations of spondyloarthritis in patients with and without the HLA-B*27 were performed, but the results revealed great heterogeneity. Objectives: The aim of this study was to evaluate the clinical manifestations of spondyloarthritis according to the classification criteria of the European Study Group Spondyloarthropathy (ESSG) in the presence and absence of the HLA-B*27. Patients and methods: From a total of 156 patients with clinical suspicion referred for the investigation of gene HLA-B*27, 73 were diagnosed with spondyloarthritis according to the criteria of ESSG. The HLA-B*27 were identified using commercial kits (Dynal ReliTM SSO HLA-B Typing Kit, Invitrogen). Clinical data were collected from medical records of patients. The results were compared using the chi-square or Fisher exact test. The values of Odds Ratio (OR) and confidence interval of 95% were also calculated. The p-value equal to or less than 0.05 was considered significant. Results: Of the 73 selected patients, 53 (72.6%) were male and 20 (27.4%) were female. The mean age was 49.4 and did not differ between genders (p = 0337). The spondyloarthritis found among the 73 patients were: ankylosing spondylitis (n = 47; 64.4%), psoriatic spondyloarthritis (n = 9; 12.3%), undifferentiated spondyloarthritis (n = 9; 12.3%), spondyloarthritis enteropathica (n = 6; 8.2%) and reactive arthritis (n = 2; 2.7%). The average age of onset was equal to 39.1 (± 11.7) and did not differ between genders (p = 0.9057). Of the total, 35 (47.9%) patients were HLA-B*27 positive and 38 (52.1%) were negative. This gene was positively associated with ankylosing spondylitis (OR: 5.37, 95% CI: 1813-15905, p = 0.003) and negatively with spondyloarthritis enteropathica (OR: 0.07, 95% CI: 0003-1301, p = 0.025). The sacroiliitis was associated with the presence of the gene (OR: 10 552, 95% CI: 1260-88256, p = 0.014) and intestinal injury absence (OR: 0.195, 95% CI: 0038-0978, p = 0.048). Conclusions: The HLA-B * 27 was associated with ankylosing spondylitis, enteropathic but not to spondyloarthritis. The radiological signs of sacroiliitis prevailed in patients positive for HLA-B*27, while intestinal involvement was associated with the absence of this gene. especially in cases of dystrophic scoliosis. In both cases, studies with larger samples are needed to assess whether these trends are evident.
Introdução: Espondiloartrite é um grupo de doenças com características clínicas, laboratoriais e imagenológicas semelhantes. Análises das manifestações clínicas das espondiloartrites em pacientes com e sem o gene HLA-B*27 foram realizadas, mas os resultados revelaram grande heterogeneidade. Objetivos: O objetivo deste trabalho foi avaliar as manifestações clínicas das espondiloartrites utilizadas nos critérios de classificação do European Spondyloarthropathy Study Group (ESSG) na presença e na ausência do gene HLA-B*27. Casuística e método: De um total de 156 pacientes com suspeita clínica, encaminhados para investigação do gene HLA-B*27, 73 tiveram diagnóstico de espondiloartrites confirmado, de acordo com os critérios do ESSG. O gene HLA-B*27 foi identificado com o uso de kits comerciais (Dynal ReliTM SSO HLA-B Typing Kit, Invitrogen). Os dados clínicos foram colhidos dos prontuários médicos dos pacientes. Os resultados foram comparados com o uso dos testes Qui-quadrado ou o teste exato de Fisher. Os valores de Odds Ratio (OR) e intervalo de confiança a 95% também foram calculados. O valor p igual ou menor que 0,05 foi considerado significante. Resultados: Dos 73 pacientes selecionados, 53 (72,6%) eram do sexo masculino e 20 (27,4%), femininos. A média de idade foi igual a 49,4 e não diferiu entre os sexos (p=0.337). As espondiloartrites encontradas entre os 73 pacientes foram: espondilite anquilosante (n=47; 64,4%), espondiloartrite psoriásica (n=9; 12,3%), espondiloartrite indiferenciada (n=9; 12,3%), espondiloartrite enteropática (n=6; 8,2%) e artrite reativa (n=2; 2,7%). A média de idade de início dos sintomas foi igual a 39,1 (±11.7) e não diferiu entre os sexos (p=0,9057). Do total, 35 (47.9%) pacientes eram HLA-B*27 positivo e 38 (52.1%), negativos. Este gene foi associado positivamente à espondilite anquilosante (OR: 5.37; IC 95%: 1.813-15.905; p=0.003) e negativamente à espondiloartrite enteropática (OR: 0.07; IC 95%: 0.003-1.301; p=0.025). A sacroiliíte se associou à presença do gene (OR: 10.552; IC 95%: 1.260-88.256; p=0.014) e o comprometimento intestinal à ausência (OR: 0.195; IC 95%: 0.038-0.978; p=0.048). Conclusões: O gene HLA-B*27 foi associado à espondilite anquilosante, mas não à espondiloartrite enteropática. Os sinais radiológicos de sacroiliíte prevaleceram nos pacientes positivos para o gene HLA-B*27, enquanto o comprometimento intestinal foi associado à ausência deste gene.
Barthel, Christian [Verfasser], i Henning [Akademischer Betreuer] Zeidler. "Expression von Neurotrophinen und ihren Rezeptoren bei Rheumatoider Arthritis und Spondyloarthritis / Christian Barthel. Abteilung für Rheumatologie im Zentrum Innere Medizin der Medizinischen Hochschule Hannover. Betreuer: Henning Zeidler". Hannover : Bibliothek der Medizinischen Hochschule Hannover, 2012. http://d-nb.info/1023140268/34.
Pełny tekst źródłaGaspard, Cindy Jeanty. "Particularités immunobiochimiques et trafic intracellulaire de la protéine HLA-B27, molécule du complexe majeur d'histocompatibilité de classe I impliquée dans les spondylarthrites". Thesis, Paris 5, 2012. http://www.theses.fr/2012PA05T001.
Pełny tekst źródłaAnkylosing spondylitis (AS), the most common form of spondyloarthritis (SpA), is strongly associated with the MHC class I HLA-B27 molecule. Although this association has been largely studied, mechanisms of pathology remain unclear. Development of a spontaneous inflammatory disease resembling human SpA in HLA-B27 transgenic rats confirmed the direct involvement of HLA-B27 and allowed to associate disease development with high expression levels of this molecule. Moreover, the HLA-B27 protein has an enhanced propensity to misfold and form aberrant disulfide linked heavy chain oligomers in the endoplasmic reticulum and at the cell surface. The goal of my thesis work was to determine if the HLA-B27 traffic and/or its ability to form oligomers are involved in this requirement of overexpression. For that, our team has developed fusion proteins ((HLA-BYFP and HLA-BRLuc) and the BRET technique to study, in vitro, the HLA-B/HLA-B interactions. Using this experimental system, we have shown the formation of intracellular vesicles, in which misfolded/unfolded HLA-B proteins accumulated when they were highly expressed, for both AS-associated alleles (HLA-B*2702, -05, et -07) or not (HLA-B*2706, et -09, HLA-B*0702). This phenomenon is strongly pronounced for AS-associated subtypes. For high-level expression, we also observed that the AS-associated subtypes form oligomers that behave differently from those formed by the HLA-B7 control protein. This phenomenon doesn’t appear to be due to unfolded protein response (UPR) triggering and is not abrogated by proteasome inhibition