Tissue-specific antibodies in myasthenia gravis.

Vincent, Angela

doi:10.1136/jcp.s3-13.1.97

Cited by 4 publications

(3 citation statements)

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“…included in this analysis because of their importance in AChR autoantibody MG immunopathology. Given the location (thymus or circulation) associated with each tip of a lineage tree, we used a maximum parsimony algorithm (23) to determine the most parsimonious history of changes between thymus and circulation along the tree. The types of predicted changes that occurred within the trees of each repertoire were then compared to those obtained from the same trees with randomized tissue states (circulation or thymus) at the tips (60).…”

Section: B Cell Clones Populating the Thymus Persist In The Circulation Aftermentioning

confidence: 99%

“…Thymic lymphofollicular hyperplasia (20) with germinal centers is observed in ∼70% of younger MG patients (21). The thymus in these patients contains both AChR-specific IgG (22) and B cells (10) that can secrete these autoantibodies (23). Transplantation of thymus from AChR-MG patients into immunodeficient mice results in human AChR-specific autoantibody deposits at the neuromuscular junction, and subsequent manifestation of MG-like symptoms (24).…”

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confidence: 99%

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Thymus-derived B cell clones persist in the circulation after thymectomy in myasthenia gravis

Jiang

Hoehn

Lee

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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Myasthenia gravis (MG) is a neuromuscular, autoimmune disease caused by autoantibodies that target postsynaptic proteins, primarily the acetylcholine receptor (AChR) and inhibit signaling at the neuromuscular junction. The majority of patients under 50 y with AChR autoantibody MG have thymic lymphofollicular hyperplasia. The MG thymus is a reservoir of plasma cells that secrete disease-causing AChR autoantibodies and although thymectomy improves clinical scores, many patients fail to achieve complete stable remission without additional immunosuppressive treatments. We speculate that thymus-associated B cells and plasma cells persist in the circulation after thymectomy and that their persistence could explain incomplete responses to resection. We studied patients enrolled in a randomized clinical trial and used complementary modalities of B cell repertoire sequencing to characterize the thymus B cell repertoire and identify B cell clones that resided in the thymus and circulation before and 12 mo after thymectomy. Thymus-associated B cell clones were detected in the circulation by both mRNA-based and genomic DNA-based sequencing. These antigen-experienced B cells persisted in the circulation after thymectomy. Many circulating thymus-associated B cell clones were inferred to have originated and initially matured in the thymus before emigration from the thymus to the circulation. The persistence of thymus-associated B cells correlated with less favorable changes in clinical symptom measures, steroid dose required to manage symptoms, and marginal changes in AChR autoantibody titer. This investigation indicates that the diminished clinical response to thymectomy is related to persistent circulating thymus-associated B cell clones.

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Section: B Cell Clones Populating the Thymus Persist In The Circulation Aftermentioning

confidence: 99%

mentioning

confidence: 99%

Thymus-derived B cell clones persist in the circulation after thymectomy in myasthenia gravis

Jiang

Hoehn

Lee

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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“…Anti-AChR antibodies are the principal agents in the pathogenesis of MG [1][2][3][4][5]20]. However, recent studies indicate that muscle components other than the AChR may also be involved in the autoimmune process of MG. Myasthenic patients with thymoma are known to have serum antibodies directed against skeletal muscle components which can be detected by various techniques such as IF [9-12, 21, 22], complement fixation [23], antiglobulin consumption [24,25], indirect haemagglutination [18,26,27], immunodiffusion [28][29][30], and an enzyme-linked immunosorbent assay [15,31,32].…”

Section: Discussionmentioning

confidence: 99%