Increased frequency of thymic T follicular helper cells in myasthenia gravis patients with thymoma

Song, Yang; Zhou, Lei; Mao, Feng; Chen, Gang; Zhu, Yaping; Gao, Xue; Wang, Yiqing; Pang, Liewen; Zhao, Chongbo; Sun, Xiaotian; Chen, Zhiming

doi:10.21037/jtd.2016.03.03

Cited by 37 publications

(25 citation statements)

References 30 publications

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“…The altered thymic function causes an increase in the release of autoreactive CD4+ and CD8+ T-cells and leads to altered T-cell subset balance [239,241,268,269,270,271]. T follicular helper cells, which play a role in B-cell selection and survival in GCs, were increased in numbers [272,273]. Th17 cells play a role in inflammation and tissue injury in autoimmunity [274], and may also play a role in MG [275,276,277,278,279,280].…”

Section: Pathogenic Effects and Origin Of Autoantibodiesmentioning

confidence: 99%

Myasthenia Gravis: Pathogenic Effects of Autoantibodies on Neuromuscular Architecture

Koneczny

Herbst

2019

Cells

119

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Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction (NMJ). Autoantibodies target key molecules at the NMJ, such as the nicotinic acetylcholine receptor (AChR), muscle-specific kinase (MuSK), and low-density lipoprotein receptor-related protein 4 (Lrp4), that lead by a range of different pathogenic mechanisms to altered tissue architecture and reduced densities or functionality of AChRs, reduced neuromuscular transmission, and therefore a severe fatigable skeletal muscle weakness. In this review, we give an overview of the history and clinical aspects of MG, with a focus on the structure and function of myasthenic autoantigens at the NMJ and how they are affected by the autoantibodies’ pathogenic mechanisms. Furthermore, we give a short overview of the cells that are implicated in the production of the autoantibodies and briefly discuss diagnostic challenges and treatment strategies.

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Section: Pathogenic Effects and Origin Of Autoantibodiesmentioning

confidence: 99%

Myasthenia Gravis: Pathogenic Effects of Autoantibodies on Neuromuscular Architecture

Koneczny

Herbst

2019

Cells

119

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“…Clinical severity of the disease (subjects with generalized MG versus subjects with ocular MG and controls) is correlated with higher mRNA expression of four markers by thymoma cells (CXCR5, Bcl-6, ICOS, and IL-21) ( 163 ). Higher percentages of thymic Tfh cells are present in MG patients, as compared to patients with thymoma without MG or patients with healthy thymus (control thymic biopsies from cardiac surgery cases) ( 164 ).…”

Section: Neurological Diseasesmentioning

confidence: 99%

T Follicular Helper Cells in Autoimmune Disorders

et al. 2018

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T follicular helper (Tfh) cells are a distinct subset of CD4+ T lymphocytes, specialized in B cell help and in regulation of antibody responses. They are required for the generation of germinal center reactions, where selection of high affinity antibody producing B cells and development of memory B cells occur. Owing to the fundamental role of Tfh cells in adaptive immunity, the stringent control of their production and function is critically important, both for the induction of an optimal humoral response against thymus-dependent antigens but also for the prevention of self-reactivity. Indeed, deregulation of Tfh activities can contribute to a pathogenic autoantibody production and can play an important role in the promotion of autoimmune diseases. In the present review, we briefly introduce the molecular factors involved in Tfh cell formation in the context of a normal immune response, as well as markers associated with their identification (transcription factor, surface marker expression, and cytokine production). We then consider in detail the role of Tfh cells in the pathogenesis of a broad range of autoimmune diseases, with a special focus on systemic lupus erythematosus and rheumatoid arthritis, as well as on the other autoimmune/inflammatory disorders. We summarize the observed alterations in Tfh numbers, activation state, and circulating subset distribution during autoimmune and some other inflammatory disorders. In addition, central role of interleukin-21, major cytokine produced by Tfh cells, is discussed, as well as the involvement of follicular regulatory T cells, which share characteristics with both Tfh and regulatory T cells.

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“…Now it is well understood that CD4 T cells differentiate into Tfh cells upon expression of the master transcription factor B‐cell lymphoma 6 (Bcl6) and surface marker CXCR5, allowing migration into the germinal center where they support differentiation of B cells into memory B cells and antibody‐secreting subsets (plasmablasts and plasma cells) . In the thymus of patients with MG, the frequency of Tfh cells and B cells increased along with the expression of the Tfh‐associated markers, IL‐21, PD‐1, and ICOS on thymocytes . CXCR5 + CD4 T cells are also found in the periphery, and it is suspected that they are memory Tfh cells that have migrated out of the germinal center .…”

Section: B‐cell‐mediated Mg Immunopathology Influenced By T Cellsmentioning

confidence: 99%

B cells in the pathophysiology of myasthenia gravis

et al. 2017

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Myasthenia gravis (MG) is an archetypal autoimmune disease. The pathology is characterized by autoantibodies to the acetylcholine receptor (AChR) in most patients or to muscle-specific tyrosine kinase (MuSK) in others and to a growing number of other postsynaptic proteins in smaller subsets. A decrease in the number of functional AChRs or functional interruption of the AChR within the muscle end plate of the neuromuscular junction is caused by pathogenic autoantibodies. Although the molecular immunology underpinning the pathology is well understood, much remains to be learned about the cellular immunology contributing to the production of autoantibodies. This Review documents research concerning the immunopathology of MG, bringing together evidence principally from human studies with an emphasis on the role of adaptive immunity and B cells in particular. Proposed mechanisms for autoimmunity, which take into account that different types of MG may incorporate divergent immunopathology, are offered. Muscle Nerve 57: 172-184, 2018.

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Increased frequency of thymic T follicular helper cells in myasthenia gravis patients with thymoma

Cited by 37 publications

References 30 publications

Myasthenia Gravis: Pathogenic Effects of Autoantibodies on Neuromuscular Architecture

Myasthenia Gravis: Pathogenic Effects of Autoantibodies on Neuromuscular Architecture

T Follicular Helper Cells in Autoimmune Disorders

B cells in the pathophysiology of myasthenia gravis

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