Survivin as a Potential Mediator to Support Autoreactive Cell Survival in Myasthenia Gravis: A Human and Animal Model Study

Abstract

The mechanisms that underlie the development and maintenance of autoimmunity in myasthenia gravis are poorly understood. In this investigation, we evaluate the role of survivin, a member of the inhibitor of apoptosis protein family, in humans and in two animal models. We identified survivin expression in cells with B lymphocyte and plasma cells markers, and in the thymuses of patients with myasthenia gravis. A portion of survivin-expressing cells specifically bound a peptide derived from the alpha subunit of acetylcholine receptor indicating that they recognize the peptide. Thymuses of patients with myasthenia gravis had large numbers of survivin-positive cells with fewer cells in the thymuses of corticosteroid-treated patients. Application of a survivin vaccination strategy in mouse and rat models of myasthenia gravis demonstrated improved motor assessment, a reduction in acetylcholine receptor specific autoantibodies, and a retention of acetylcholine receptor at the neuromuscular junction, associated with marked reduction of survivin-expressing circulating CD20+ cells. These data strongly suggest that survivin expression in cells with lymphocyte and plasma cell markers occurs in patients with myasthenia gravis and in two animal models of myasthenia gravis. Survivin expression may be part of a mechanism that inhibits the apoptosis of autoreactive B cells in myasthenia gravis and other autoimmune disorders.

Thymoma related myasthenia gravis in humans and potential animal models

“…Comparing clinical, histological, immunologic and genetic features in early-onset myasthenia gravis (EOMG), late-onset myasthenia gravis (LOMG) and thymoma-associated myasthenia gravis (TAMG) (as reviewed in [36] and[140]). AIRE = autoimmune regulator; APS-I = autoimmune polyendocrine syndrome type I; mTEC = medullary thymic epithelial cells; adjacent LFH = lymphofollicular hyperplasia in the remnant thymus adjacent to the thymoma.…”

Complement associated pathogenic mechanisms in myasthenia gravis

“…А также принимает участие в реализации адаптивных иммунных реакций, контролирует дифференцировку Т-клеток памяти CD4 +и CD8+ и созревание В-клеток. В литературе имеются сведения о возможном применении сурвивина в качестве диагностического и прогностического маркера при ревматоидном артрите, псориазе, легочной артериальной гипертензии, рассеянном склерозе, воспалительных заболеваниях кишечника, миастении гравис [36,56]. По мнению ряда ученых, компоненты системы комплемента участвуют в блокировании нервно-мышечной передачи, которое клинически проявляется развитием мышечной утомляемости.…”

Phosphorylation Modulates Survivin Function in Behcet’s Disease

“…Up-regulation of BIRC5 in autoimmune diseases is reported in recent studies. 4,7,10,21 High BIRC5 level is found in PBMCs of patients with rheumatoid arthritis (RA), 12 myasthenia gravis 21 and multiple sclerosis. 22 We first analyzed BIRC5 gene expression levels in PBMCs by quantitative PCR analysis.…”