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Статті в журналах з теми "Multiple Sclerosis, Biomarkers, Immune response"
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Mathur, Deepali, Bikash Kumar Mishra, Soumyashree Rout, Francisco Jose Lopez-Iranzo, Gerardo Lopez-Rodas, Jayalakshmi Vallamkondu, Ramesh Kandimalla, and Bonaventura Casanova. "Potential Biomarkers Associated with Multiple Sclerosis Pathology." International Journal of Molecular Sciences 22, no. 19 (September 25, 2021): 10323. http://dx.doi.org/10.3390/ijms221910323.
Повний текст джерелаАнотація:
Multiple sclerosis (MS) is a complex disease of the central nervous system (CNS) that involves an intricate and aberrant interaction of immune cells leading to inflammation, demyelination, and neurodegeneration. Due to the heterogeneity of clinical subtypes, their diagnosis becomes challenging and the best treatment cannot be easily provided to patients. Biomarkers have been used to simplify the diagnosis and prognosis of MS, as well as to evaluate the results of clinical treatments. In recent years, research on biomarkers has advanced rapidly due to their ability to be easily and promptly measured, their specificity, and their reproducibility. Biomarkers are classified into several categories depending on whether they address personal or predictive susceptibility, diagnosis, prognosis, disease activity, or response to treatment in different clinical courses of MS. The identified members indicate a variety of pathological processes of MS, such as neuroaxonal damage, gliosis, demyelination, progression of disability, and remyelination, among others. The present review analyzes biomarkers in cerebrospinal fluid (CSF) and blood serum, the most promising imaging biomarkers used in clinical practice. Furthermore, it aims to shed light on the criteria and challenges that a biomarker must face to be considered as a standard in daily clinical practice.
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Puentes, Fabiola, Pascal Benkert, Sandra Amor, Jens Kuhle, and Gavin Giovannoni. "Antibodies to neurofilament light as potential biomarkers in multiple sclerosis." BMJ Neurology Open 3, no. 2 (November 2021): e000192. http://dx.doi.org/10.1136/bmjno-2021-000192.
Повний текст джерелаАнотація:
Background and objectiveThe concentration of neurofilament light (NfL) protein in cerebrospinal fluid (CSF) and blood is widely considered as a quantitative measure of neuro-axonal injury. Immune reactivity to NfL released into extracellular fluids induces specific autoantibody response. We investigated the levels and avidity of antibodies to NfL in patients with multiple sclerosis (MS) treated with disease-modifying therapies (DMTs) and their correlation with disease worsening and NfL protein concentration.MethodsWe conducted a prospective longitudinal study in 246 patients with MS (125 DMT-treated and 121 untreated at baseline). Serum levels of NfL antibodies, antibody avidity and immune complexes were determined by ELISA. NfL protein was measured using the Simoa platform. Clinical variables were tested for their association with the measured parameters in multivariate generalised estimating equation models.ResultsMultivariate analysis showed that levels of NfL antibodies were higher in progressive MS compared with clinically isolated syndrome (CIS)/relapsing remitting multiple sclerosis (RRMS) (p=0.010). Anti-NfL levels drop with increasing disability score (Expanded Disability Status Scale (EDSS)) (p=0.002), although conversely, were significantly elevated in CIS/RRMS after a recent EDSS increase (p=0.012). Patients receiving DMTs showed decreased levels of anti-NfL (p=0.008), high-avidity antibodies (p=0.017) and immune-complexes compared with untreated CIS/RRMS. Patients with MS switching to natalizumab showed lower levels of anti-NfL but higher immune complexes compared with healthy controls (p=0.0071). A weak association was observed between the levels of NfL protein and NfL antibodies.ConclusionsThese results support the potential usefulness of quantifying antibody response to NfL as potential markers of progression and treatment response in MS and need to be considered when interpreting peripheral blood NfL levels.
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Mycko, Marcin P., and Sergio E. Baranzini. "microRNA and exosome profiling in multiple sclerosis." Multiple Sclerosis Journal 26, no. 5 (January 22, 2020): 599–604. http://dx.doi.org/10.1177/1352458519879303.
Повний текст джерелаАнотація:
New DNA sequencing technologies have uncovered non-coding RNA (ncRNA) as a major player in regulating cellular processes and can no longer be dismissed as “junk” or “dark” RNA. Among the ncRNA, microRNA (miRNA) is arguably the most extensively characterized category and a number of studies have implicated them in regulating critical functions that can influence autoimmune demyelination. Of specific interest to multiple sclerosis (MS), miRNA have been implicated in both regulating immune responses and myelination, thus making them an attractive candidate for both pharmacological intervention and as disease biomarkers. In addition, exosomes, small vesicles secreted by most cell types and present in all body fluids, have been also shown to play roles in immune signaling, inflammation and angiogenesis. Therefore, exosomes are also being explored as tools for therapeutic delivery and as biomarkers. This article reviews the recent advances in miRNA and exosome profiling in MS and experimental models.
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Bose, Gauruv, Simon D. X. Thebault, Harold L. Atkins, and Mark S. Freedman. "Does Resetting the Immune System Fix Multiple Sclerosis?" Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques 47, no. 1 (October 18, 2019): 1–10. http://dx.doi.org/10.1017/cjn.2019.294.
Повний текст джерелаАнотація:
Abstract:Multiple sclerosis is the leading non-traumatic cause of disability in young adults, affecting up to 100,000 Canadians. This chronic inflammatory and neurodegenerative disease of the central nervous system leads to irreversible neurologic disability if inadequately controlled. Though many current medications are available that reduce inflammatory damage, most patients continue to show some evidence of disease activity and accrue disability. In this review, we discuss the role of immune ablation followed by autologous hematopoietic stem cell transplantation (AHSCT), a therapeutic option for select patients with a more aggressive disease course. By “resetting” the immune system with a variety of ablative conditioning regimens, followed by immune reconstitution, this therapy has shown a durable response in halting evidence of inflammatory activity in most patients, without the need for continued disease-modifying therapies (DMT). Since the introduction of this therapy, there have been advances in patient selection and supportive care, such that morbidity has significantly declined and treatment-related mortality is minimized. Recent phase-II trials have shown excellent results in efficacy and safety of AHSCT; however, challenges exist which require ongoing study. The future challenges include comparing the variety of AHSCT conditioning regimens with each other as well as with existing highly effective DMT; identifying patients with an aggressive disease course through novel biomarkers who may benefit the most from AHSCT; and surveillance of long-term outcomes of different treatment protocols. In select patients, replacing the immune system with AHSCT holds promise of fundamentally altering the trajectory of their aggressive disease course.
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Feki, Sawsan, Salma Sakka, Sabrina Mejdoub, Mariem Damak, Hend Hachicha, Chokri Mhiri, and Hatem Masmoudi. "Biomarkers related to the intrathecal humoral immune response as laboratory tools for multiple sclerosis diagnosis." Journal of the Neurological Sciences 429 (October 2021): 118168. http://dx.doi.org/10.1016/j.jns.2021.118168.
Повний текст джерела
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Harris, Violaine K., Nicola Donelan, Qi Jiang Yan, Kristi Clark, Amir Touray, Mustapha Rammal, and Saud A. Sadiq. "Cerebrospinal fluid fetuin-A is a biomarker of active multiple sclerosis." Multiple Sclerosis Journal 19, no. 11 (February 25, 2013): 1462–72. http://dx.doi.org/10.1177/1352458513477923.
Повний текст джерелаАнотація:
Background: There is an urgent need for biomarkers in multiple sclerosis (MS) that can reliably measure ongoing disease activity relative to inflammation, neurodegeneration, and demyelination/remyelination. Fetuin-A was recently identified as a potential biomarker in MS cerebrospinal fluid (CSF). Fetuin-A has diverse functions, including a role in immune pathways. Objective: The objective of this research is to investigate whether fetuin-A is a direct indicator of disease activity. Methods: We measured fetuin-A in CSF and plasma of patients with MS and correlated these findings to clinical disease activity and natalizumab response. Fetuin-A expression was characterized in MS brain tissue and in experimental autoimmune encephalomyelitis (EAE) mice. We also examined the pathogenic role of fetuin-A in EAE using fetuin-A-deficient mice. Results: Elevated CSF fetuin-A correlated with disease activity in MS. In natalizumab-treated patients, CSF fetuin-A levels were reduced one year post-treatment, correlating with therapeutic response. Fetuin-A was markedly elevated in demyelinated lesions and in gray matter within MS brain tissue. Similarly, fetuin-A was elevated in degenerating neurons around demyelinated lesions in EAE. Fetuin-A-deficient mice demonstrated delayed onset and reduced severity of EAE symptoms. Conclusions: Our results show that CSF fetuin-A is a biomarker of disease activity and natalizumab response in MS. Neuronal expression of fetuin-A suggests that fetuin-A may play a pathological role in the disease process.
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Gutiérrez-Fernández, María, Fernando de la Cuesta, Antonio Tallón, Inmaculada Cuesta, Mireya Fernández-Fournier, Fernando Laso-García, Mari Carmen Gómez-de Frutos, Exuperio Díez-Tejedor, and Laura Otero-Ortega. "Potential Roles of Extracellular Vesicles as Biomarkers and a Novel Treatment Approach in Multiple Sclerosis." International Journal of Molecular Sciences 22, no. 16 (August 20, 2021): 9011. http://dx.doi.org/10.3390/ijms22169011.
Повний текст джерелаАнотація:
Extracellular vesicles (EVs) are a heterogeneous group of bilayer membrane-wrapped molecules that play an important role in cell-to-cell communication, participating in many physiological processes and in the pathogenesis of several diseases, including multiple sclerosis (MS). In recent years, many studies have focused on EVs, with promising results indicating their potential role as biomarkers in MS and helping us better understand the pathogenesis of the disease. Recent evidence suggests that there are novel subpopulations of EVs according to cell origin, with those derived from cells belonging to the nervous and immune systems providing information regarding inflammation, demyelination, axonal damage, astrocyte and microglia reaction, blood–brain barrier permeability, leukocyte transendothelial migration, and ultimately synaptic loss and neuronal death in MS. These biomarkers can also provide insight into disease activity and progression and can differentiate patients’ disease phenotype. This information can enable new pathways for therapeutic target discovery, and consequently the development of novel treatments. Recent evidence also suggests that current disease modifying treatments (DMTs) for MS modify the levels and content of circulating EVs. EVs might also serve as biomarkers to help monitor the response to DMTs, which could improve medical decisions concerning DMT initiation, choice, escalation, and withdrawal. Furthermore, EVs could act not only as biomarkers but also as treatment for brain repair and immunomodulation in MS. EVs are considered excellent delivery vehicles. Studies in progress show that EVs containing myelin antigens could play a pivotal role in inducing antigen-specific tolerance of autoreactive T cells as a novel strategy for the treatment as “EV-based vaccines” for MS. This review explores the breakthrough role of nervous and immune system cell-derived EVs as markers of pathological disease mechanisms and potential biomarkers of treatment response in MS. In addition, this review explores the novel role of EVs as vehicles for antigen delivery as a therapeutic vaccine to restore immune tolerance in MS autoimmunity.
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Zhou, Qingqing, Rui Jia, and Jingxia Dang. "Correlation between the Neutrophil-to-Lymphocyte Ratio and Multiple Sclerosis: Recent Understanding and Potential Application Perspectives." Neurology Research International 2022 (October 26, 2022): 1–10. http://dx.doi.org/10.1155/2022/3265029.
Повний текст джерелаАнотація:
Multiple sclerosis (MS) is a chronic debilitating immune-mediated disease of the central nervous system, which causes demyelination and neuroaxonal damage. Low-grade systemic inflammation has been considered to lead to pathogenesis owing to the amplification of pathogenic immune response activation. However, there is a shortage of reliable systemic inflammatory biomarkers to predict the disease activity and progression of MS. In MS patients, a series of cytokines and chemokines promote the proliferation of neutrophils and lymphocytes and their transfer to the central nervous system. The neutrophil-to-lymphocyte ratio (NLR), which combines the information of the inherent and adaptive parts of the immune system, represents a reliable measure of the inflammatory burden. In this review, we aimed to discuss the inflammatory response in MS, mainly the function of lymphocytes and neutrophils, which can be implemented in the utility of NLR as a diagnostic tool in MS patients. The underlying pathophysiology is highlighted to identify new potential targets for neuroprotection and to develop novel therapeutic strategies.
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Mechelli, Rosella, Silvia Romano, Carmela Romano, Emanuele Morena, Maria Chiara Buscarinu, Rachele Bigi, Gianmarco Bellucci, et al. "MAIT Cells and Microbiota in Multiple Sclerosis and Other Autoimmune Diseases." Microorganisms 9, no. 6 (May 24, 2021): 1132. http://dx.doi.org/10.3390/microorganisms9061132.
Повний текст джерелаАнотація:
The functions of mucosal-associated invariant T (MAIT) cells in homeostatic conditions include the interaction with the microbiota and its products, the protection of body barriers, and the mounting of a tissue-repair response to injuries or infections. Dysfunction of MAIT cells and dysbiosis occur in common chronic diseases of inflammatory, metabolic, and tumor nature. This review is aimed at analyzing the changes of MAIT cells, as well as of the microbiota, in multiple sclerosis and other autoimmune disorders. Common features of dysbiosis in these conditions are the reduced richness of microbial species and the unbalance between pro-inflammatory and immune regulatory components of the gut microbiota. The literature concerning MAIT cells in these disorders is rather complex, and sometimes not consistent. In multiple sclerosis and other autoimmune conditions, several studies have been done, or are in progress, to find correlations between intestinal permeability, dysbiosis, MAIT cell responses, and clinical biomarkers in treated and treatment-naïve patients. The final aims are to explain what activates MAIT cells in diseases not primarily infective, which interactions with the microbiota are potentially pathogenic, and their dynamics related to disease course and disease-modifying treatments.
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Król-Grzymała, Angelika, Edyta Sienkiewicz-Szłapka, Ewa Fiedorowicz, Dominika Rozmus, Anna Cieślińska, and Andrzej Grzybowski. "Tear Biomarkers in Alzheimer’s and Parkinson’s Diseases, and Multiple Sclerosis: Implications for Diagnosis (Systematic Review)." International Journal of Molecular Sciences 23, no. 17 (September 4, 2022): 10123. http://dx.doi.org/10.3390/ijms231710123.
Повний текст джерелаАнотація:
Biological material is one of the most important aspects that allow for the correct diagnosis of the disease, and tears are an interesting subject of research because of the simplicity of collection, as the well as the relation to the components similar to other body fluids. In this review, biomarkers for Alzheimer’s disease (AD), Parkinson’s disease (PD), and multiple sclerosis (MS) in tears are investigated and analyzed. Records were obtained from the PubMed and Google Scholar databases in a timeline of 2015–2022. The keywords were: tear film/tear biochemistry/tear biomarkers + diseases (AD, PD, or MS). The recent original studies were analyzed, discussed, and biomarkers present in tears that can be used for the diagnosis and management of AD, PD, and MS diseases were shown. α-synTotal and α-synOligo, lactoferrin, norepinephrine, adrenaline, epinephrine, dopamine, α-2-macroglobulin, proteins involved in immune response, lipid metabolism and oxidative stress, apolipoprotein superfamily, and others were shown to be biomarkers in PD. For AD as potential biomarkers, there are: lipocalin-1, lysozyme-C, and lacritin, amyloid proteins, t-Tau, p-Tau; for MS there are: oligoclonal bands, lipids containing choline, free carnitine, acylcarnitines, and some amino acids. Information systematized in this review provides interesting data and new insight to help improve clinical outcomes for patients with neurodegenerative disorders.
Дисертації з теми "Multiple Sclerosis, Biomarkers, Immune response"
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Ghadiri, Mahtab. "Peripheral Immune Phenotyping in Multiple Sclerosis: Immunomodulatory Treatment Effects and Treatment Response Biomarkers." Thesis, The University of Sydney, 2019. http://hdl.handle.net/2123/20809.
Повний текст джерелаАнотація:
Disease modifying therapies (DMTs) used in the treatment of relapsing remitting multiple sclerosis (RRMS) have broad effects on the immune system that are incompletely understood. There is great heterogeneity in treatment response to most DMTs. However, biomarkers predicting treatment response are lacking. In this thesis, the peripheral immune changes induced by treatment with two DMTs, fingolimod (FTY) and dimethyl fumarate (DMF), are examined in detail by immune phenotyping using multicolour flow cytometry. Chapter 3 presents a longitudinal study of T cell subsets in patients commencing treatment with DMF. Differential losses of T cell subsets are found, including relative changes in regulatory and effector subsets potentially relevant to the mechanism of action of DMF. DMF-induced lymphopaenia is further studied in an in vitro culture system. The study results suggest that differential susceptibility of distinct T cell subsets to DMF-induced apoptosis may underly differential T cell losses seen in treated patients. In Chapter 4, the effects of FTY on peripheral T cell subsets and the reversibility of these effects is explored in patients ceasing FTY treatment. Long-lasting alterations in circulating T cell subsets are documented, indicating that FTY-induced changes in the peripheral immune repertoire may persist beyond the time taken for clinical laboratory measures to normalise. Chapter 5 presents a longitudinal study of a broad range of immune cell subsets in patients commencing FTY. Changes in potentially disease-relevant immune cell subsets not previously examined in FTY-treated patients are documented. Using magnetic resonance imaging (MRI) and clinical information to assess disease activity in these patients, potential immune biomarkers of FTY treatment response are uncovered. This thesis expands on our understanding of the effects of MS DMTs on the peripheral immune repertoire and highlights the utility of immune phenotyping in exploring DMT mechanisms of action and treatment response biomarkers.
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Rathbone, Emma. "Investigation of the adaptive immune response in multiple sclerosis." Thesis, University of Birmingham, 2018. http://etheses.bham.ac.uk//id/eprint/8510/.
Повний текст джерелаАнотація:
In multiple sclerosis (MS), clonally-expanded brain-resident B cells may sustain chronic disease, however their relative contributions versus recently recruited B cells is unclear. Furthermore, pro-inflammatory CD20+ T cells may also be involved in MS pathogenesis. This study aimed to characterise the cerebrospinal fluid (CSF) B cell response in MS and investigate the features of CD20+ T cells. CSF B cells and antibody-secreting cells (ASC) displayed an activated phenotype and were identified in MS CSF at a higher frequency than controls. In contrast to the periphery, CSF ASC almost exclusively expressed IgG and were strongly lgK-biased, whereas memory B cells displayed similar immunoglobulin expression profiles in both compartments. MS CSF antibodies were frequently reactive towards EBNA-1, which preferentially induced an lgK-biased antibody response. Finally, CD20+ T cells displayed a highly activated effector phenotype and were present in the CSF, although their frequencies were no different between MS and OND groups. These findings suggest that most CSF B cells result from non-specific recruitment, whereas ASC are involved in a persistent lgK-biased antigen-driven immune response, which may primarily be directed towards EBNA-1. Despite their highly activated phenotype, a role for CD20+ T cells in MS pathogenesis, if any, remains to be determined.
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Malhotra, Sunny 1984. "Search of prognostic biomarkers in patients with multiple sclerosis." Doctoral thesis, Universitat Pompeu Fabra, 2014. http://hdl.handle.net/10803/129852.
Повний текст джерелаАнотація:
The aim of the thesis was to identify biomarkers for multiple
sclerosis (MS) prognosis, in particular disease activity biomarkers
and interferon-β (IFNβ) treatment response biomarkers. The results
presented in this thesis show an increase in the expression of sialic
acid binding Ig-like lectins 1 (SIGLEC1) in progressive phases of
MS (particularly during primary progressive MS - PPMS). Detailed
analysis has demonstrated that both inflammatory and resident
monocytes contributed to increased SIGLEC1 expression in PPMS.
We also reported that SIGLEC7 expression was elevated in
relapsing-remitting MS (RRMS) patients during relapses. Our
results also indicate deficient expression of ubiquitin specific
peptidase 18 (USP18) in RRMS patients as compared to controls.
Further investigation revealed that haplotype CG carriers showed
lower USP18 gene expression levels and higher clinical disease
activity compared to CG non-carriers. Moreover, AA homozygosis
for an intronic polymorphism of USP18 was associated with the
responder phenotype. In conclusion, our results suggest the
implication of SIGLEC1 in chronic progressive phases of MS and
of SIGLEC7 in acute disease activity. We also demonstrated the
implication of USP18 in MS pathogenesis and the therapeutic
response to IFNβ. Based on these results, we propose SIGLEC1,
SIGLEC7 and USP18 as potential disease activity biomarkers of
MS, and USP18 as response biomarker to IFNβ.El objetivo de esta tesis ha sido la identificación de biomarcadores pronósticos en la esclerosis múltiple (EM), principalmente biomarcadores de actividad de la enfermedad y biomarcadores de respuesta al tratamiento con interferón beta (IFNβ). Los resultados expuestos en esta tesis muestran un incremento en la expresión del gen “sialic acid binding Ig-like lectins 1” (SIGLEC1) en fases progresivas de la EM (principalmente en pacientes con EM primariamente progresiva - EMPP). Un análisis más detallado demostró que tanto los monocitos residentes como los inflamatorios contribuyeron al incremento de la expresión de SIGLEC1 en pacientes con EMPP. También observamos que la expresión de SIGLEC7 se encuentró aumentada en la EM recurrente-remitente (EMRR) durante el brote. Nuestros resultados también mostraron una expresión deficiente del gen “ubiquitin specific peptidase 18” (USP18) en pacientes con EMRR comparado con controles. Experimentos adicionales mostraron que los pacientes portadores del haplotipo CG presentaron niveles de expresión del gen USP18 disminuidos y un incremento en la actividad clínica de la enfermedad en comparación con los no portadores del haplotipo CG. Además, los pacientes homocigotos AA para un polimorfismo intrónico del gen USP18 presentaron una buena respuesta al tratamiento con IFNβ. En conclusión, nuestros resultados sugieren la implicación de SIGLEC1 en la fase crónica progresiva de la EM, y un papel de SIGLEC7 en la actividad aguda de la enfermedad. También sugieren la implicación de USP18 en la patogenia de la EM y la respuesta terapéutica al IFNβ. En base a estos resultados, proponemos SIGLEC1, SIGLEC7 y USP18 como biomarcadores de actividad de la enfermedad, y USP18 como biomarcador de respuesta al IFNβ.
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McCarthy, Claire Louise. "Peripheral blood cytokine profiles of multiple sclerosis patients & the immune response of multiple sclerosis patients treated with alemtuzumab." Thesis, University of Cambridge, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.609204.
Повний текст джерела
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Gomes, Andreia Ferreira de Castro. "Regulation of lymphocyte activation and apoptosis in the immune response in multiple sclerosis /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7349-910-2/.
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Lidén, Ellinor. "Multiple sclerosis – is a dysregulated immune response the route to illness via Epstein-Barr virus reactivation?" Thesis, Linnéuniversitetet, Institutionen för kemi och biomedicin (KOB), 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-96858.
Повний текст джерелаАнотація:
Background: Throughout human history infectious agents such as viruses have been one of the biggest threats to public health. One example of infectious agents that can cause severe malignant conditions in humans is the Epstein-Barr virus (EBV). This virus has been researched for decades but still a lot of its potential malignant functions remain to be elucidated. Autoimmunity, and especially multiple sclerosis (MS), has been strongly associated to EBV infection for a long time but the exact mechanisms behind this relationship are still largely unknown. Aim: The main aim of this study was to investigate the evidence connecting an EBV-specific dysregulated immune response to MS. Methods: This paper is written as a systematic review examining the latest science within the studied field. PubMed was searched for articles published between 2010-2020. Results: In total 15 studies were reviewed. Five out of seven studies found an altered antibody response towards EBV in patients with MS, while one demonstrated somewhat mixed results and one could not support such a pattern. Seven out of eight studies found an altered T cell response towards EBV in MS patients, while one could only support such a trend. Conclusions: This review confirms that there is strong evidence for a dysregulated EBV-specific immune response in MS patients. Evidence for a causal relationship between the failure to control a reactivated EBV infection and the progression of disease is suggestive, but this needs to be confirmed by further studies.
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Buhler, Marc McWilliams. "Genetics of the immune cell receptors TCRB and CCR5 in human disease." University of Sydney, 2003. http://hdl.handle.net/2123/601.
Повний текст джерелаАнотація:
Abstract Early in the evolution of the vertebrates it is thought that two genomic duplications occurred, providing a basis for the evolution in body plan and neural crest of very early vertebrates and substantive material for further evolution of various gene families such as those making up a number of components of the adaptive vertebrate immune system. While the bony fish possibly had another, genome duplications are not generally a feature of vertebrate evolution and indeed the appearance of an antigen-adaptive immune recognition system may have served to limit the size that various vertebrate genomes, including that of the human, can in fact achieve. This initial step in vertebrate immune evolution, the establishment of recognition of non-self against the unique set of 'self' epitopes for an individual, provided an immensely powerful weapon in immune function with the ability to tailor a defense against as-yet-unseen dangers at any time albeit with the pitfall of autoimmune disease. As the recognition sites of the antigen receptor molecules such as TcR are produced by clonal modification of the segments provided in the germline and are thus not in the genome itself, pathogens have not been able to hijack this one component of the immune system in the way so many other components have been put to use throughout evolution, nor do these components necessarily reveal themselves as associated with disease through genome screens. Importantly, overall immune function is determined not just by the potential repertoire of recognition receptors but also by the ability of immunocompetent cells to migrate in a tissue specific fashion through the use of various chemokines and their receptors. Typical of the hijacking of an immune system component by a pathogen is the use of a chemokine ligand gene in the viral ancestor to SIV and HIV, allowing for virus binding to immunocompetent cells as is seen in the use of the CCR5 chemokine receptor by macrophage-tropic HIV strains. This thesis describes the allele and genotype frequencies for several TcR beta-chain variable segment polymorphisms in a population of MS patients compared with controls before and after stratification for HLA-DR15, polymorphism in the Apo-1 / Fas promoter, the DRB1 Val86/Val86 genotype, CCR5-delta32 and the HLA-DRA promoter. The thesis continues with CCR5-delta32 genotyping in IDDM, MS and SLE cohorts and then examines the question of the population of origin of the delta-32 allele of the CCR5 receptor for chemokine. Here, a case / control comparison of 122 RR-MS patients with 96 normal individuals was made for allele and genotype frequencies and for haplotypes formed by pairs of TCRB markers. Further analysis was made after HLA-DR15 stratification. Linkage disequilibrium was found between pairs of alleles of bv8s1, bv10s1, bv15s1 and bv3s1 loci in both patients and controls. In the RR-MS cohort, an increase in the allele frequency of bv8s1*2 was seen (p = 0.03) and the haplotype bv8s1*2 / bv3s1*1 was increased (p = 0.006), and both were found to be statistically significant. In the DR15-positive group, association between MS and TCRB was seen with the bv8s1*2 allele (p = 0.05) and the bv8s1*2 / bv10s1 haplotypes (p = 0.048), while the haplotype associations seen among the DR15-negative patients included the bv3s1*1 allele (bv10s1*1 / bv3s1*1, p = 0.022; bv8s1*2 / bv3s1*1, p = 0.048). While no associations were found after stratification for SDF1-3'A, Apo-1 / Fas or DRB1 there were modest interactions between bv3s1, bv10s1 and bv15s1 and the HLA-DRA promoter. These results support the involvement of the TCRB region in MS susceptibility. The further study of autoimmune disease here includes genotype analysis of CCR5-delta32 in type 1 diabetes (IDDM) and SLE. CCR5 is the major co-receptor for viral entry used by macrophage-tropic HIV strains and protection from infection is seen in homozygotes for CCR5-delta32. In diabetes, infiltration of pancreatic tissue by autoreactive T-cells involves secretion of multiple cytokines and chemokine receptor expression. Variation in the chemokine receptor CCR5 may result in differences in inflammatory cell migration in response to relevant chemokines. Adolescents with type 1 diabetes were genotyped for CCR5-delta32 (n = 626). The allele frequency was compared with that of 253 non-diabetic adolescents and with that of 92 adults with SLE. A reduced allele frequency was seen in type 1 diabetes compared with controls (0.092 vs 0.123, p = 0.05). This difference was not seen for the cohort of patients with SLE (freq = 0.114). A reduction in the number of CCR5-delta32/delta32 homozygotes, who lack CCR5, in the type 1 diabetes cohort was also seen and while not statistically significant (2 observed compared to 5.25 expected; p = 0.12) is interesting. These results suggest a partial protection from type 1 diabetes for CCR5-delta32 homozygous individuals is possible and that CCR5 has a potential role in the pathogenesis of type 1 diabetes. Global surveys of the CCR5-delta32 allele have confirmed a single mutation event in a Northeastern European population as the source of this allele. Here, Australian Ashkenazi Jews (n = 807) were found to have a CCR5-delta32 allele frequency of 14.6% while Australian Sephardic Jews (n = 35) had a frequency of 5.7% and non-Jewish Australian controls (n = 311) had an allele frequency of 11.25%. Data on birthplace of grandparents showed a gradient with highest CCR5-delta32 frequencies from Eastern European Ashkenazim (~19.5% for those whose four grandparents come only from Russia, Poland, Hungary, Austria and Czechoslovakia; n = 197) which differs significantly from the frequency seen in Ashkenazi Jews from Western Europe (n = 101, p = 0.001). Homozygotes for CCR5-delta32 were genotyped with 3p21 region microsatellites. This has defined an ancestral haplotype on which the mutation first occurred and helped to date this event to between 40 and 50 generations ago or just over a thousand years ago. The population gradient, combined with the dating of the mutation by microsatellite allele frequencies, suggests an origin for the CCR5-delta32 allele in a population ancestral to the Ashkenazim. The distribution in non-Jewish populations in northern Europe has led others to postulate spread of the mutation by Vikings. It is hypothesised here that the link between the two populations could be the kingdom of Khazaria with subsequent admixture into both Swedish Vikings and Ashkenazi Jews. The basic driving force of evolution is through selection and the immune system has a role which, through the survival pressure exerted by viruses and other pathogens, has the potential to exert a great deal of selective force on the various components of this system. The effects of this pronounced selection on an immune system component can be seen for example in the increase of the CCR5-delta32 allele over the last thousand years to the current frequency. As mentioned, some immune system components are not affected by such straightforward selection. In the case of the TCRBV segments, effects on the immune repertoire can occur through MHC interaction at the point of thymic entry and in the effects of various superantigens, but the actual binding pockets that recognise antigen are themselves unable to be selected for (or against). The findings presented in this thesis provide support for the association of TCRBV gene segments with multiple sclerosis and also provide support for the further study of the role of the CCR5-delta32 allele in type 1 diabetes. Furthermore, data presented here suggests that the CCR5-delta32 allele had an origin in the Khazar Kingdom just over a thousand years ago, accounting for the allele frequencies in both the Ashkenazi Jews and in lands frequented by the Vikings. The definition of an extended ancestral haplotype for the CCR5-delta32 allele shows how the effect of selection of an allele of one gene can carry with it specific alleles of a large number of other genes as well.
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Powell, Nicole Damico. "Immunomodulation of experimental autoimmune encephalomyelitis targeting the autoreactive T cell and the cytokine macrophage migration inhibitory factor /." Columbus, Ohio : Ohio State University, 2006. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1141052089.
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Champy-Tixier, Anne-Sophie. "Extraction, purification, and structurala nalysis of glycosylated natural products, mimetics of native antigens involved in an immune response." Thesis, Bourgogne Franche-Comté, 2018. http://www.theses.fr/2018UBFCE003/document.
Повний текст джерелаАнотація:
Cette these en cotutelle entre le Laboratoire Peptlab de l’Université de Florence en Italie et le Laboratoire de Pharmacognosie de l’Université de Bourgogne Franche-Comté en France, porte sur l’extraction, la purification et l’élucidation structurale de saponines d’origine végétale en tant que mimétiques d’antigènes impliqués dans une réponse immunitaire. L’étude phytochimique de cinq espèces végétales appartenant à trois familles différentes, Fabaceae : Wisteria frustecens, Wisteria floribunda “macrobotrys”, Wisteria floribunda “rosea”, Caprifoliaceae : Weigela florida “rumba” et Polygalaceae : Polygala acicularis, a conduit à l’isolement de seize glycosides triterpéniques naturels parmi lesquelles six sont de structure nouvelle, une a été isolée sous sa forme native pour la première fois, et neuf déjà répertoriées dans la littérature. Les composés ont été isolés grâce à l’utilisation de différentes méthodes chromatographiques. Leurs structures ont été élucidées en utilisant principalement la RMN 2D et la spectrométrie de masse. Parmis ces seize molécules, six ont été sélectionnées pour être testées en tant que mimétiques d’antigènes impliqués dans une réponse immunitaire. De plus, un flavonoïde glycosylé extrait de Sophora japonica et un acide triterpénique commercial, l’acide ursolique, ont eux aussi été choisis comme mimétiques d’antigènes. Des tests immunochimiques (ELISA) ont été réalisés afin d’évaluer leur potentiel en tant que mimétiques d’antigènes dans le sang de patients atteints de sclérose en plaque ou du syndrome de Rett. Le taux IgM dans le sérum des patients atteints de sclérose en plaque ou du syndrome de Rett a été mesuré et comparé à celui de donneurs sains. Concernant la sclérose en plaque, les résultats sont peu significatifs concernant le potentiel des saponines en tant que mimétiques d’antigènes. Mais dans le cas du syndrome de Rett des résultats intéressants et surprenants ont été obtenus. En effet, l’hypothèse de départ était l’implication de la partie glycosylée dans la reconnaissance d’autoanticorps. Pour le syndrome de Rett, l’acide ursolique, qui est un aglycone, démontre une grande efficacité dans la reconnaissance d’IgM. Par contre, un triterpène glycosylé démontre lui aussi une efficacité semblable. Les résultats obtenus sont donc à analyser afin d’établir des relations structure/activité fiablesThis PhD in co-direction between the Peptlab Laboratory of the University of Firenze (Italy) and the Laboratory of Pharmacognosy of the University of Bourgogne Franche-Comté (France), deals with extraction, purification and structural elucidation of saponins from plants as mimetic antigens involved in an immune response. The phytochemical study of five species from three different families, Wisteria frustecens, Wisteria floribunda “macrobotrys” and Wisteria floribunda “rosea” from Fabaceae, Weigela florida “rumba” from Caprifoliaceae, and Polygala acicularis from Polygalaceae, allowed us to isolate sixteen natural glycosides: six with new structures, one analyzed for the first time in its native form, and nine which have been already described in the literature. These compounds were isolated using various chromatographic methods, and their structures were elucidated using mainly 2D NMR and mass spectrometry. From the isolated glycosides, six were selected and tested as mimetics of native antigens involved in the immune response. Moreover, one flavonoid glycoside extracted from Sophora japonica, and one commercial triterpenic acid, ursolic acid, were also chosen as mimetics of native antigens. Immunoenzymatic assays (ELISA) were performed for each compound to evaluate their potential as mimetics of native antigens of multiple sclerosis and Rett syndrome. The IgM levels in sera of patients affected by multiple sclerosis and Rett syndrome were measured and compared to normal blood donors. Concerning multiple sclerosis, no significant results were obtained for saponins, but in the case of Rett syndrome, interesting and surprising results were obtained. Indeed, the first hypothesis was that the glycosyl part of the molecule could be relevant for antibody recognition. In the case of Rett syndrome ursolic acid, an aglycone without any glycosidic part, demonstrated a good efficiency in IgM recognition. On the other hand, one triterpenic glycoside showed similar results. These results were discussed to define possible structure/activity relationships
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Mazziotti, Valentina. "Exploring promising biomarkers in multiple sclerosis." Doctoral thesis, 2023. https://hdl.handle.net/11562/1082370.
Повний текст джерелаАнотація:
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS), affecting 2.3 million people worldwide, of which approximately 122,000 are in Italy. MS represents a multifactorial disease, typical of in young adulthood, whose cause is still unknown. An important role in the MS pathogenesis, seems to be played by inflammatory processes affecting the CNS associated with neurodegenerative phenomena with consequent alteration or loss of sensory, motor and cognitive functions. The characteristics of the inflammation and axonal damage that occur in MS, determined different disease forms: a relapsing-remitting form and a progressive form. The two forms of MS are distinguished according to the course of the disease. The first is characterized by an alternation of acute episodes of disease, alternating with periods without symptoms; the second, consists in a persistent and progressive disability. To date, there are no prognostic clinical and neuroradiological tools for MS. Consequently, it is not not being able to identify, since from the time of diagnosis, patients with a high risk of presenting a more severe disease course, makes the therapeutic choice difficult for the clinician and risky for the patient. In this scenario, identifying new diagnostic, prognostic and predictive markers of disease, through the use of advanced molecular technologies, is of fundamental importance. The aim of this thesis was to identify new biomarkers associated with a high risk of disease activity, through an exploratory analysis of the CSF levels of specific cytokines and pro-inflammatory chemokines associated with the activation of lymphocyte and microglial cells, underly the pathogenesis mechanisms of MS, and investigate the prognostic role of several biomarkers recognized in MS, whose validity is still debated (CXCL13, IgM, Nf-L, PVALB), evaluating the association between intrathecal (meningeal and CSF) and peripheral inflammation. The results obtained allowed to identify a CSF profile associated with a high risk of disease activity, characterized by high molecules levels released by activated T (IFNγ and TNFα), B (LIGHT, APRIL, CXCL13, CXCL12, LIGHT) and microglial cells (sCD163). Furthermore, biomarkers analysis, in combination with clinical and radiological evaluation, confirming an early compartmentalized intrathecal inflammation at the level, in MS patients at high risk of disease activity, already at the time of diagnosis. Finally, given the recent COVID-19 pandemic, a specific study on the antibody and cell-mediated response by MS patients treated with different immunosuppressive therapies (cladribin, fingolimod and ocrelizumab) was included in this thesis. The study demonstrated a different vaccine effect in patients treated with different treatments: patients receiving ocrelizumab showed an impaired antibody production and, on the contrary, a preserved cell-mediated response, associated with an inflammatory mediators production.
Книги з теми "Multiple Sclerosis, Biomarkers, Immune response"
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Compston, Alastair. Multiple sclerosis and other demyelinating diseases. Oxford University Press, 2011. http://dx.doi.org/10.1093/med/9780198569381.003.0871.
Повний текст джерелаАнотація:
The oligodendrocyte–myelin unit subserves saltatory conduction of the nerve impulse in the healthy central nervous system. At one time, many disease processes were thought exclusively to target the structure and function of myelin. Therefore, they were designated ‘demyelinating diseases’. But recent analyses, based mainly on pathological and imaging studies, (re)emphasize that axons are also directly involved in these disorders during both the acute and chronic phases. Another ambiguity is the extent to which these are inflammatory conditions. Here, distinctions should be made between inflammation, as a generic process, and autoimmunity in which rather a specific set of aetiological and mechanistic conditions pertain. And there are differences between disorders that are driven primarily by immune processes and those in which inflammation occurs in response to pre-existing tissue damage.With these provisos, the pathological processes of demyelination and associated axonal dysfunction often account for episodic neurological symptoms and signs referable to white matter tracts of the brain, optic nerves, or spinal cord when these occur in young people. This is the clinical context in which the possibility of ‘demyelinating disease’ is usually considered by physicians and, increasingly, the informed patient. Neurologists will, with appropriate cautions, also be prepared to diagnose demyelinating disease in older patients presenting with progressive symptoms implicating these same pathways even when there is no suggestive past history. Both in its typical and atypical forms multiple sclerosis remains by far the commonest demyelinating disease. But acute disseminated encephalomyelitis, the leucodystrophies, and central pontine myelinolysis also need to be considered in particular circumstances; and multiple sclerosis itself has a differential diagnosis in which the relapsing-remitting course is mimicked by conditions not associated with direct injury to the axon–glial unit. Since our understanding of the cause, pathogenesis and features of demyelinating disease remains incomplete, classification combines aspects of the aetiology, clinical features, pathology, and laboratory components. Whether the designation ‘multiple sclerosis’ encapsulates one or more conditions is now much debated. We anticipate that a major part of future studies in demyelinating disease will be further to resolve this question of disease heterogeneity leading to a new taxonomy based on mechanisms rather than clinical empiricism. But, for now, the variable ages of onset, unpredictable clinical course, protean clinical manifestations, and non-specific laboratory investigations continue to make demyelinating disease one of the more challenging diagnostic areas in clinical neurology.
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Freedman, Mark S., and Mohammad Abdoli. The Importance and Utility of Cerebrospinal Fluid Evaluation in the Diagnosis of Central Demyelinating Diseases. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199341016.003.0008.
Повний текст джерелаАнотація:
This chapter aims to highlight the diagnostic and prognostic value of cerebrospinal fluid (CSF) findings in multiple sclerosis with a special consideration of distinguishing it from neuromyelitis optica (NMO) and NMO spectrum disorder. Interpretation of CSF findings in daily clinical practice in patients with MS is thoroughly explained. New advances in CSF analysis and recently identified biomarkers may be helpful for diagnosis, help elucidate disease subtype and activity, or aid in prognosis and monitoring of the response to treatment. Characteristics of CSF changes in different subtypes of multiple sclerosis, clinically isolated syndrome (CIS), and radiologically isolated syndrome (RIS) are discussed. CSF findings in NMO spectrum disease as a diagnostic and differentiating marker are explained separately.
Частини книг з теми "Multiple Sclerosis, Biomarkers, Immune response"
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Viel, Riccardo. "Multiple Sclerosis and Zoster Encephalomyelitis: a Probable Common Etiopathogenesis." In The Immune Response to Viral Infections, 289–91. Boston, MA: Springer US, 1989. http://dx.doi.org/10.1007/978-1-4684-5712-4_31.
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Zaffaroni, Mauro, Silvano Rossini, Rosalia Palma, Angelo Ghezzi, Stellio Marforio, and Carlo L. Cazzullo. "Loss of Suppressor-inducer T-Cells in Chronic-progressive Multiple Sclerosis: Preliminary Results." In The Immune Response to Viral Infections, 293–95. Boston, MA: Springer US, 1989. http://dx.doi.org/10.1007/978-1-4684-5712-4_32.
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Gheuens, J. "Idiotypes in the Immune Response to Measles Virus." In Cellular and Humoral Immunological Components of Cerebrospinal Fluid in Multiple Sclerosis, 103–9. Boston, MA: Springer US, 1987. http://dx.doi.org/10.1007/978-1-4899-5348-3_13.
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Reiber, H. "Evaluation of blood cerebrospinal fluid barrier function and quantification of the humoral immune response within the central nervous system." In Cerebrospinal Fluid Analysis in Multiple Sclerosis, 51–72. Milano: Springer Milan, 1996. http://dx.doi.org/10.1007/978-88-470-2205-8_5.
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Lassmann, Hans. "Immune Response in the Human Central Nervous System in Multiple Sclerosis and Stroke." In Neuroinflammation, 1–19. Hoboken, NJ, USA: John Wiley & Sons, Inc, 2015. http://dx.doi.org/10.1002/9781118732748.ch1.
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Dörries, Rüdiger, Rihito Watanabe, Helmut Wege, and Volker ter Meulen. "Analysis of the Intrathecal Humoral Immune Response in Corona Virus Induced Encephalomyelitis of Rats." In Cellular and Humoral Immunological Components of Cerebrospinal Fluid in Multiple Sclerosis, 37–46. Boston, MA: Springer US, 1987. http://dx.doi.org/10.1007/978-1-4899-5348-3_6.
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Rudick, Richard A. "Free Light Chains of Immunoglobulins in Multiple Sclerosis: A Putative Index of the Intrathecal Humoral Immune Response." In Cellular and Humoral Immunological Components of Cerebrospinal Fluid in Multiple Sclerosis, 187–200. Boston, MA: Springer US, 1987. http://dx.doi.org/10.1007/978-1-4899-5348-3_23.
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Ignatova, Valentina. "Biomarkers in Multiple Sclerosis." In Multiple Sclerosis - Genetics, Disease Mechanisms and Clinical Developments [Working Title]. IntechOpen, 2022. http://dx.doi.org/10.5772/intechopen.106052.
Повний текст джерелаАнотація:
Clinical, biological, and radiological evidence are currently needed to diagnose MS, but lack of preclinical biomarkers hinders the earliest possible diagnosis and treatment. Conventional biomarkers target immunity, blood-brain barrier disruption, demyelination, and neuronal and axonal damage, as well as mitochondrial activity. An increase of specific brain metabolites with 30–40% is registered before detection of MRI lesions in MS. Potential lipid biomarkers are fatty acids, phospholipids, and oxysterols. The role of proteoforms in the pathogenesis of MS was confirmed. Serum neurofilament light chains (sNfL) are currently being studied as a readily available biomarker for prognosis and response to treatment in MS. The sNfL levels reflect ongoing neuroaxonal damage caused by inflammation, and the sNfL levels predict disease activity over the next few years. The retinal nerve fiber layer (RNFL) thinning is reliable as a biomarker of disability worsening. The neutrophil-to-lymphocyte ratio and CRP are also MS biomarkers. The development of rationally targeted therapeutic agents that allow preventive treatment to stop the disease is also delayed without definite biomarkers.
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"Neuronal control of the immune response in the CNS: implications on neuronal cell death and survival." In Multiple Sclerosis, 29–37. CRC Press, 2001. http://dx.doi.org/10.3109/9780203212974-8.
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Singh, Sanjay, Sukanya Tripathy, and Anand Prakash. "Multiple Sclerosis: Molecular Biology, Pathophysiology and Biomarkers." In Neurodegenerative Diseases - Multifactorial Degenerative Processes, Biomarkers and Therapeutic Approaches (First Edition), 115–24. BENTHAM SCIENCE PUBLISHERS, 2022. http://dx.doi.org/10.2174/9789815040913122010010.
Повний текст джерелаАнотація:
In the brain, multiple sclerosis is a chronic disease caused by immunemediated neurodegeneration. About 2.5 million people around the world suffer from multiple sclerosis (MS), and women are more prone to it. Neither clinical nor imaging biomarkers are used to diagnose or characterize the disease. Molecular biomarkers have been developed from immunology and neurobiology because they are well matched with causal path mechanisms and other disease characteristics, thus, limiting the number of molecular biomarkers used in clinical practice. Currently, the chapter discusses the attribute of flawless MS biomarkers and the challenges associated with developing newer biomarkers. The study also discusses the discovery of biomarkers from the blood and cerebrospinal fluid (CSF) that are useful for diagnosing MS, predicting its prognosis, and evaluating its therapeutic response and side effects.
Тези доповідей конференцій з теми "Multiple Sclerosis, Biomarkers, Immune response"
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Rezende, Karla Viana, Ayrton Senna do Brasil Amaral Alves, Juliana Carollyne Amorim, Maria Inês Vaz de Oliveira, Maria Paula Banhara Rodrigues, and Vitor Matias Grah. "Helminth-induced immune response: A new perspective for the treatment of Multiple Sclerosis." In XIII Congresso Paulista de Neurologia. Zeppelini Editorial e Comunicação, 2021. http://dx.doi.org/10.5327/1516-3180.603.
Повний текст джерелаАнотація:
Background: Multiple Sclerole (MS) is a progressive neurodegenerative disease that, in its most common form, evolves in outbreaks and compromises the patient’s quality of life and functionality. In a long time, a way of attenuating symptoms and preventing the progression of this pathology has been studied, however, drug therapies, until now, have not shown good accuracy. In this context, the exogenous use of helminths as non-drug therapy for MS has been considered, therefore, this study aims to demonstrate the recent results of studies on such therapies and verify whether there is scientific evidence of a good clinical, immunological and exam response. image of patients with MS. Methods: Bibliographic review in the PUBMED database Results: The four large studies carried out on the topic demonstrated evidence that the immune response induced by helminths decreases the activity of the immunological factors that contribute to the progression of MS, however the small control groups and unfavorable environments impaired the conclusions of the studies . Conclusions: Although the studies have no yet to demonstrate reliable clinical evidence about exogenous helminth therapy, it is undeniable that the good immune response induced by the parasites is a great hope that motivates the continuation of studies in the area.
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Barreto, Maria Eduarda Slhessarenko Fraife, Arthur Malzyner, Nelson Hamerschlak, Maurício Muradian, Alessandra Delavance, and Lívia Almeida Dutra. "Myasthenia gravis, myositis, myocarditis and anti-titin antibodies after Nivolumab/Ipilimumab: response with plasmapheresis." In XIII Congresso Paulista de Neurologia. Zeppelini Editorial e Comunicação, 2021. http://dx.doi.org/10.5327/1516-3180.379.
Повний текст джерелаАнотація:
Context: Severe neurological manifestations following use of immune checkpoint inhibitors (ICIs) occur in 0.93% of patients, and together with cardiac toxicity have the higher lethality. Myasthenia gravis (MG) and polymyositis (PM) are rare, and treatment includes discontinuation of the immunotherapy, corticosteroids, and intravenous immunoglobulin (IVIG), with occasional use of plasmapheresis (PLEX). Biomarkers are not consistently reported. We report the case of a patient with MG, PM and myocarditis after ICI, with positive anti-titin antibodies and response to plasmapheresis. Case report: 81-year-old male developed ascending, subacute, progressive tetraparesis, dysphagia, ophthalmoparesis, and respiratory failure 2 weeks after second cycle of nivolumab/ipilimumab for metastatic melanoma. Physical examination showed: globally reduced strength, hypoactive reflexes, bilateral sixth nerve palsy and bilateral semi-ptosis. Prostigmine test was positive and electroneuromyography was compatible with myopathy. Labs revealed CPK 4000 U/L, troponin 9000U/L, autoimmune myositis panel negative, anti-titin antibodies (described in paraneoplastic MG and associated with severity) positive and cardiac MRI without fibrosis. Clinical picture was compatible with MG and PM with cardiac involvement. He received methylprednisolone and six PLEX sessions, with complete recovery. Four months after treatment, he developed cognitive impairment and large B-cell lymphoma (ICI complication). Conclusions: PM and MG may occur after ICI, especially in the first cycles, and anti-titin may be a biomarker of severity in these patients. Although guidelines recommend adding IVIG or PLEX in refractory or severe cases, PLEX may be first choice, especially if multiple ICI are present.