[CITATION][C] Antibody Effector Mechanisms in Myasthenia Gravis: The Complement Hypothesisa

DP Richman, MA Agius, CA Kirvan… - Annals of the New …, 1998 - Wiley Online Library
DP Richman, MA Agius, CA Kirvan, CM Gomez, RH Fairclough, BL Dupont, RA Maselli
Annals of the New York Academy of Sciences, 1998Wiley Online Library
Myasthenia gravis (MG) and experimental autoimmune myasthenia gravis (EAMG) are
autoimmune diseases in which disordered neuromuscular transmission is the result of
autoantibody-induced damage to the acetylcholine receptor (AChR)–containing
postsynaptic end plate membrane. While an anti-AChR T cell response (primarily CD4+
cells) is crucial in MG and EAMG, the role of these cells appears to be solely to provide help
to the antibody-producing B cells. We have used monoclonal antibodies (mAbs) to study the …
Myasthenia gravis (MG) and experimental autoimmune myasthenia gravis (EAMG) are autoimmune diseases in which disordered neuromuscular transmission is the result of autoantibody-induced damage to the acetylcholine receptor (AChR)–containing postsynaptic end plate membrane. While an anti-AChR T cell response (primarily CD4+ cells) is crucial in MG and EAMG, the role of these cells appears to be solely to provide help to the antibody-producing B cells. We have used monoclonal antibodies (mAbs) to study the antibody effector mechanisms involved in disease pathogenesis. A wide array of data suggests that the major mechanism involves very efficient complement activation as a result of antibodies bound to the very densely packed (almost crystalline) AChR molecules normally present in the peaks of the end plate synaptic folds. To test the predominant role of complement activation in the pathogenesis of MG and EAMG, we have examined a number of model systems in which complement activation is absent or reduced. Because these systems involve a number of possibly confounding variables, we have engineered recombinant/hybrid antibodies with modified CH regions that poorly fix complement, with the goal of testing the ability of these antibodies to induce EAMG or to prevent the disease induced by antibodies that are effective in activating complement.
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