Theoretical mechanisms by which immunoglobulin therapy might benefit myasthenia gravis.

The mechanisms underlying any clinical improvement observed in some patients with myasthenia gravis (MG) treated with normal immunoglobulin (Ig) are not defined. The pathologic alterations in the postsynaptic motor end plate in MG are likely due at least in part to one or more actions of antibodies against epitopes on the nicotinic acetylcholine receptor (anti-AChR Ab). Such anti-AChR Ab are secreted by B lymphocytes and are increased in the serum of MG patients but not of controls. The stimulus for anti-AChR Ab production in MG is unknown with evidence for a role of thymic abnormalities, immunoregulatory disturbances, and some possible molecular mimicry of exogenous antigens (microbial?). Postulated mechanisms underlying Ig effects in MG include: (i) competing with anti-AChR for binding to AChR; (ii) preventing attachment of Fc receptor-positive inflammatory cells to the anti-AChR Ab bound to the motor end plate; (iii) decreasing synthesis of anti-AChR Ab; and (iv) exerting an anti-idiotypic effect. Evidence for these mechanisms are discussed.