Date of Award

Spring 2021

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Immunobiology

First Advisor

Kleinstein, Steven

Abstract

Myasthenia gravis (MG) is an autoimmune neuromuscular disorder caused by autoantibodies that disrupt neuromuscular transmission by targeting components of neuromuscular junctions, such as the acetylcholine receptor (AChR, 90% of patients) and muscle specific kinase (MuSK, 10% of patients). Treatments that address the underlying causes of MG target the cells responsible for producing these autoantibodies. Two such treatment strategies are predominantly used: (1) surgical resection of the thymus (a reservoir for auto-antigen specific B cells in patients with AChR MG) and (2) systemic therapy targeting subsets of autoantibody-producing B cells. The thymus is a known anatomic reservoir for B cells that can produce pathogenic AChR autoantibodies, and resection of the thymus has long been known to improve MG symptoms. However, many patients also fail to achieve complete remission after thymectomy. Rituximab (RTX) is a B cell depleting agent used in the management of an increasingly wide range of autoimmune diseases. Many AChR and MuSK MG patients achieve remission after RTX but relapse following treatment cessation can occur for some patients. In both cases, I was interested in testing the possibility that the failed depletion of B cells relevant to disease may drive poor responses.

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