Myasthenia Gravis
The major focus of our research efforts are directed toward understanding myasthenia gravis (MG). Over the last 10 years at Yale, our group has formed a coordinated, multidisciplinary program that aims to answer fundamental questions with respect to the immunopathology of MG. We demonstrated that B cell depletion therapy has sustained efficacy in MG. We showed that MG-derived AChR antigen specific T cells belong to the pro-inflammatory Th17 subset. We recently determined that MG subjects harbor defects in B cell tolerance checkpoints that correlate with abnormalities in the naive B cells repertoire. Most recently, we identified the autoantibody-producing cells in MuSK MG, then produced a library of human MuSK-specific monoclonal antibodies (mAbs). These findings represent fundamental contributions to autoimmunity in MG that had not been previously realized. Since embarking on our investigation to understand the mechanism of MG immunopathology, we have sought to isolate and identify only the specific cells that produce the autoantibodies. While this goal presented challenges, our collective efforts paid off. We now have the ability to identify and isolate these rare cells from which we have produced a series of human MG monoclonal autoantibodies (mAbs). These mAbs have begun to provide unprecedented insight into the details of MG autoimmune mechanisms.
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