Anti-C2-mediated complement inhibition prevents disease in a rat passive transfer model of myasthenia gravis.

Acetylcholine receptor antibody-positive myasthenia gravis (AChR-MG) is a rare autoimmune disease in which AChR autoantibodies trigger complement activation and cause damage to the neuromuscular junction. This study evaluated the therapeutic potential of an anti-C2 antibody in the rat passive transfer model of myasthenia gravis (PTMG). Female Lewis rats (n = 36) were prophylactically treated with either an anti-rat C2 antibody or an IgG isotype control 2 h prior to subcutaneous injection of mAb35 (PTMG) or saline (non-MG). Serum samples were collected at several timepoints during the study and muscle weakness; body weight and clinical manifestations were assessed daily. The animals underwent electromyography prior to euthanasia. AChR content in the tibialis anterior was determined by radioimmunoassay. Anti-C2 antibody-treated animals maintained body weight, grip strength and muscle AChR content (both functional and total) at levels comparable to non-MG animals. Serum analyses confirmed reduced complement activity over the course of the experiment in anti-C2 treated animals. These findings indicate that anti-C2 treatment effectively prevents disease development in this model, supporting its potential as a therapeutic strategy for managing AChR-MG.