Myasthenia gravis

Abstract

To clarify the role of cell-mediated versus humoral immune effector responses in myasthenia gravis (MG), we examined the occurrence of inflammatory cells in muscle from 30 patients with MG, determined the site of accumulation of the cells (at or remote from end-plates), enumerated and immunophenotyped those cells at the end-plate, and evaluated the frequency of deposition of the complement membrane attack complex (MAC) at the end-plate. Seven of 30 patients had well-defined collections of mononuclear cells in muscle (lymphorrhages), but these were not topographically related to the end-plates. Twenty of 30 patients had inflammatory cells (mostly macrophages and T cells) at or near end-plates, but these cells were present at less than 10% of the end-plates, and only seldom was there more than one cell at any end-plate. None of the inflammatory cells penetrated the muscle fiber near the end-plate. All end-plates of all patients immunostained for MAC. The findings reconfirm that the predominant immune effector response in MG is humorally mediated. The lymphorrhages in muscle and other tissues are probably a nonspecific indicator of disturbed immune regulation in MG.

Current Treatment, Emerging Translational Therapies, and New Therapeutic Targets for Autoimmune Myasthenia Gravis

“…Pathology studies have demonstrated complement deposition in the motor endplate region in AChR MG [126][127][128]. In addition, the autoantibodies in AChR MG are predominantly IgG1 and IgG3, which are known to activate complement [129,130].…”

CCL2 recruitment of IL‐6‐producing CD11b+ monocytes to the draining lymph nodes during the initiation of Th17‐dependent B cell‐mediated autoimmunity

“…In MG and EAMG, major immune effectors of the disease process at the neuromuscular junctions are circulating IgG autoantibodies reactive to AChR, whereas the cellular inflammatory infiltrates in the muscles are sparse and not considered essential for the impaired neuromuscular transmission, both in humans and mice [16,19,20]. Therefore, we measured anti-murine AChR IgG (and related isotypes) in CCL2 -/-mice and control mice immunized Figure 1.…”

Effect of complement and its regulation on myasthenia gravis pathogenesis

“…In human MG, the strongest evidence for complement as a pathogenic mechanism derives from identification of antibody, C3 and MAC deposition at neuromuscular junctions from MG patients [5][6][7]. Depletion of serum complement components, C3 and C4 is observed in patients, but their levels are not related to severity of weakness [47].…”

“…In 1977, Engel appreciated the binding of complement components to the endplates of MG patients [5][6][7] and experimentally acquired MG (EAMG) animals [8]. Since then, the role of complement in the initiation, progression and susceptibility of the disease has been investigated as to the structural alterations of the neuromuscular junction and the systemic changes that occur to the immune system.…”