Online PhD conferral Miriam F. L. Fichtner
Supervisors: Prof. Dr. Pilar Martinez, Prof. Dr. Kevin C. O’Connor
Co-supervisor: Dr. Mario Losen
Keywords: Myasthenia gravis, autoantibodies, B cell depletion therapy, relapse
"Features of muscle-specific tyrosine kinase autoantibodies and B cells derived from myasthenia gravis patients"
Autoimmunity is a malfunction of the immune system where an immune response develops against one’s own tissues. Myasthenia gravis (MG) is an autoimmune disease in which the immune system causes impairment of neuromuscular function by producing autoantibodies that interrupt signaling from nerves to muscles. This thesis examined the mechanism of relapse in MG patients after treatment with the B cell-depleting therapy, rituximab. It is not known whether the autoantibodies of MG patients in relapse are generated from new autoreactive B cell clones or pre-existing B cell clones that persisted through treatment. This thesis investigated the pathogenic capacity of six monoclonal patient-derived autoantibodies and found that MuSK-specific B cells present during post-rituximab relapse emerge from the unsuccessful depletion of pre-existing B cell clones, demonstrating that rituximab is not fully effective at eliminating autoantibody-producing B cells and providing a mechanistic understanding of post-rituximab relapse.
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