The complement system plays a key role in MG, most evidence of which being drawn from animal models of the disease. Anti-AChR antibodies belong to the complement-fixing immunoglobulin (Ig) G1 and IgG3 subclasses, and their pathogenicity is mainly owing to complement system activation.
The alternative pathway is triggered by foreign pathogens and polymeric IgA. The lectin pathway is activated by binding of mannose-binding lectin to microbial pathogens and may involve IgA-containing immune complexes.
The complement cascade comprises over 30 proteins found in the plasma and on cell surfaces. The consequential steps are cleavage of C3 into C3a and C3b, and of C5 in C5a and C5b, the latter leading to membrane attack complex (MAC) formation. MACs are lipophilic protein complexes that insert into cell membranes, resulting in pore formation and eventually cell lysis of nonnucleated cells and damage to nucleated cells. Anticomplement drugs are emerging as effective therapies to treat patients with AChR MG. Eculizumab inhibits C5 cleavage into C5a and C5b, thereby blocking MAC formation.
Learn more about the pathophysiology of MG.
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Cite this: Raghav Govindarajan, Nicholas J. Silvestri. Fast Five Quiz: Pathophysiology of Myasthenia Gravis - Medscape - Sep 15, 2023.