Pathogenic Autoantibodies in AChR-Negative Myasthenia Gravis

Antibodies directed against the nicotinic acetylcholine receptor (AChR) are found in approximately 80% of patients with generalized myasthenia gravis (GMG). A substantial number of the seronegative GMG patients have anti–muscle-specific kinase (MuSK) antibodies, but some GMG patients harbor neither of these antibodies. Investigators hypothesized that patients with neither antibody might have antibodies against LDL receptor–related protein 4 (Lrp4), which together with MuSK forms an essential postsynaptic ligand-receptor complex for neural agrin. Signaling through this complex is essential for clustering of AChRs and for function of the neuromuscular junction.

Using a luciferase-reporter immunoprecipitation assay, the authors found elevated t…