With the initial identification in 1976 of antibodies directed toward the acetylcholine receptor (AChR) in the serum of patients with myasthenia gravis (MG),1 it became clear that upwards of 20% of patients with clinical and electrophysiological evidence of a neuromuscular disorder lacked such antibodies. Was this because of the presence of low-affinity antibodies that were capable of disease induction but not detectable by the standard radioimmunoassay? This answer appears to be partially the case. Using cell-based assays that present the complex pentameric, membrane-bound AChR in a much more native state, AChR antibodies can be found among seronegative patients.2 However, Lindstrom et al1 suggested another possibility that antibodies may be directed toward other target antigens and produce a similar clinical and electrophysiological disorder.
Kaminski HJ. Seronegative Myasthenia Gravis—A Vanishing Disorder?. JAMA Neurol. 2016;73(9):1055-1056. doi:10.1001/jamaneurol.2016.2277