Antibody Effector Mechanisms in Myasthenia Gravis: The Complement Hypothesis^a

Treatment of Myasthenia Gravis by Preventing Acetylcholine Receptor Modulation

“…Passive transfer studies in EAMG in rats and mice have shown promise for the use of Fab fragments of anti‐AChR antibodies that compete with pathogenic IgG in protection against disease 13,42–44 . The antibody fragments exert their action through monovalent binding (.…”

Plasmaaustausch als Therapieoption bei neurologischen Erkrankungen

“…Die häufigste Form der Erkrankung wird durch zirkulierende Autoantikörper gegen den nikotinischen Acetylcholinrezeptor (AChR) hervorgerufen [59,60,61,62]. Mechanismen, die für den Verlust von funktionsfähigen AChRs und somit für die Beeinträchtigung oder Unterbrechung der sicheren neuromuskulären Erregungsübertragung verantwortlich sind, sind unter anderem der Abbau des AChR [63], die komplementvermittelte Lyse von AChR [64] und die Interferenz mit der Neurotransmitterbindung [65]. In Untergruppen AChR-Antikörper-negativer Patienten können andere Antikörper unterschiedlicher Spezifität nachgewiesen werden, beispielsweise Antikörper gegen muskelspezifische Rezeptor-Tyrosinkinase (MuSK) [66,67].…”

Treatment Principles in the Management of Autoimmune Myasthenia Gravis

“…All four subunits are homologous, with an extracellular portion, a membrane‐spanning region that contributes to the lining of the ion channel, and an intracellular portion. Both T helper cells and B cells are involved in the autoimmune response, but the effector arm of the immune response solely comprises anti‐AChR antibodies 1–3. That is, whereas T cells play a crucial role in this disease, the attack upon the neuromuscular junction is carried out exclusively by antibodies.…”

“…The first of these is so‐called antigenic modulation (increased turnover) induced by cross‐linking of adjacent AChR molecules by a single bivalent antibody molecule. This mechanism also appears to play a relatively minor role as well 1,8. It is the third effector mechanism of these autoantibodies that appears to be the most effective in reducing neuromuscular transmission.…”

“…These destructive changes are mediated primarily through activation of the complement cascade. The complement activation in MG produces both the membrane attack complex, which lyses the membrane to which the antibody is bound, and chemotactic products, which attract inflammatory macrophages 1,9–11…”