MG is characterized by a detrimental humoral response against key proteins on the neuromuscular junction, including the acetylcholine receptor (AChR) and muscle-specific tyrosine kinase (MuSK). In about 10% of MG patients, defined as seronegative, a lack of detectable autoantibodies by radioimmunoassay hampers a prompt diagnosis and restricts eligibility for clinical trials and payers’ reimbursement for certain therapies. In variable proportions of SNMG patients, autoantibodies can be detected by cell-based assays (CBA). However, data on CBA positivity rates in the U.S. are lacking. Moreover, the prevalence of low-density lipoprotein receptor-related protein 4 (LRP4) autoantibodies, and the presence of autoantibodies against yet unidentified muscle autoantigens, remain uncertain in SNMG.

Of 99 SNMG samples tested by CBA, 18 (18.2%) were positive for AChR autoantibodies; none were MuSK or LRP4 autoantibody positive. As further evidence of a positive AChR autoantibody status, circulating AChR-specific B cells were identified in a CBA-positive SNMG patient, and their specificity was validated through the isolation of a recombinant monoclonal antibody. REAP revealed potentially novel autoantibody reactivities restricted to SNMG patients.