Myasthenia gravis (MG) treatment consists largely of toxic immunosuppressive regimens used for years and utilized in a highly variable fashion among clinicians worldwide and with patients complaining of a poor quality of life. Further complicating care is the growing appreciation over the last few decades of clinical and pathophysiological heterogeneity. Presently, five distinct subgroups of MG are generally accepted to exist: 1) early-onset acetylcholine receptor (AChR) antibody (Ab) positive MG, which primarily affects women, 2) late-onset AChR Ab positive MG with a disease bias towards men 3) paraneoplastic thymoma-associated MG, 4) muscle specific kinase (MuSK) Ab positive, and 5) AChR/MuSK Ab negative MG. Only AChR Ab positive MG has been well represented in clinical trials, in large part because of a lack of knowledge about the natural history and treatment response in the other subgroups. There is a critical need to fill this knowledge gap in order to allow for future clinical trials and improve patient care. Current biomarkers available for use in the MG clinic do not predict response to immunosuppressive therapies. Comprehensive immunologic profiles over the course of treatment must be performed in large cohorts of MG patients. To address these deficiencies in research and clinical care, the MGNet RDCRN proposes the Exploring Outcomes and Characteristics of Myasthenia Gravis (EXPLORE-MG) study which will perform rigorous clinical phenotyping linked to standardized biospecimen collection. We exploit the existing biorepository developed by the PI (Neuromuscular IMmunology BiosampLE (NIMBLE) Network) created with the purpose of biomarker discovery. We will integrate and expand the existing collaborative infrastructure with a refined and extensive clinical phenotypic characterization developed by Dr. Richard Nowak at Yale University. We propose Specific Aim 1: Characterize the clinical phenotype, epidemiology, and diagnostic and management paradigms in the subgroups of MG and Specific Aim 2: Enhance an existing multi-center biospecimen collection process to support MGNet clinical projects 2 and 3, MGNet pilot studies program, and the greater MG research community.
