Serological and experimental studies in different forms of myasthenia gravis

Abstract

Antibodies to the acetylcholine receptor (AChR) have been recognized for over 40 years and have been important in the diagnosis of myasthenia gravis (MG), and its recognition in patients of different ages and thymic pathologies. The 10-20% of patients who do not have AChR antibodies are now known to comprise different subgroups, the most commonly reported of which is patients with antibodies to muscle-specific kinase (MuSK). The use of cell-based assays has extended the repertoire of antibody tests to clustered AChRs, low-density lipoprotein receptor-related protein 4, and agrin. Autoantibodies against intracellular targets, namely cortactin, titin, and ryanodine receptor (the latter two being associated with the presence of thymoma), may also be helpful as biomarkers in some patients. IgG4 MuSK antibodies are clearly pathogenic, but the coexisting IgG1, IgG2, and IgG3 antibodies, collectively, have effects that question the dominance of IgG4 as the sole pathologic factor in MuSK MG. After a brief historical review, we define the different subgroups and summarize the antibody characteristics. Experiments to demonstrate the in vitro and in vivo pathogenic roles of MuSK antibodies are discussed.

Immunopathogenesis of Myasthenia Gravis (Review)

“…В литературе описан ряд серологических маркеров, имеющих отношение к миастении [107]. Это подчеркивает многообразие механизмов пато-генеза и, возможно, служит объяснением существо-вания различий в клинических проявлениях [44,66].…”

“…Воздействие на эти клетки, по данным некоторых исследователей, перспективное направление в те-рапии аутоиммунных расстройств. По мнению ряда исследователей именно регуляторные Т-лимфоциты являются наиболее перспективными в изучении па-тогенеза миастении [97,107]. Кроме Т-клеток, В-клетки также участвуют в разви-тии миастении путем продуцирования аутоантител.…”

Autoantibodies in acquired myasthenia gravis: Clinical phenotype and immunological correlation

“…2 About 60% of subjects with ocular myasthenia and 85% with generalized MG have AChR antibodies. 4,5 In addition, antibodies directed against the skeletal and cardiac muscle are detected in some patients of MG and include those binding titin, ryanodine, Kv1.4, actin, myosin, actinin, filamin, cortactin, dihydropyridine receptor or transient receptor potential canonical type 3, among others. Among those who are "seronegative" for AChR antibodies, the most notable is the MUSK antibody.…”

“…2 Antibodies against other components of the neuromuscular junction viz MUSK, LRP4, agrin and collagen-Q are also implicated in the pathophysiology of MG. 1 While AChR antibodies are fairly well characterized, knowledge regarding other antibodies is evolving. 4,[6][7][8] Though not of diagnostic value, they are purported to have some role in predicting severity and course of MG. 4,5 In addition, antibodies directed against the skeletal and cardiac muscle are detected in some patients of MG and include those binding titin, ryanodine, Kv1.4, actin, myosin, actinin, filamin, cortactin, dihydropyridine receptor or transient receptor potential canonical type 3, among others.…”

“…They indicate additional pathological processes that alter muscle function in addition to the neuromuscular junction defect. 3,4,10 Identifying these antibodies is important as it supports the diagnosis of MG as well as aids in sub-grouping based on the immune profile. 1 The frequency of different antibodies varies among different races, genders and thymic pathologies.…”