Rinsho Shinkeigaku (Clinical Neurology)

Symposium 3

Anti-MuSK antibodies in myasthenia gravis block binding of collagen Q to MuSK

Kinji Ohno, M.D.

Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine

In myasthenia gravis (MG), 5-15% of patients are positive for MuSK antibodies. MuSK binds to LRP4 and transmits an agrin-mediated signal for clustering of acetylcholine receptor (AChR). MuSK also anchors the collagenic tail subunit (ColQ) of acetylcholinesterase (AChE). MuSK-IgG is a blocking antibody, but its molecular targets remained elusive. As acetylcholine receptor (AChR) deficiency is typically mild and as cholinesterase inhibitors are generally ineffective in MuSK-MG patients, we asked if MuSK-IgG interferes with binding of ColQ to MuSK. The in vitro overlay assay showed that MuSK-IgG blocked binding of ColQ to the neuromuscular junction of Colq-/- mice. The in vitro plate-binding assay showed that MuSK-IgG blocked binding of ColQ to MuSK in a dose-dependent manner. Passive transfer of MuSK-IgG to wild-type mice reduced the size and density of ColQ to ~10% of controls and had a lesser effect on the size and density of AChR and MuSK. These data point to a notion that MuSK-IgG blocks binding of ColQ to MuSK. As lack of ColQ compromises agrin-mediated AChR clustering in Colq-/- mice, a similar mechanism may lead to AChR deficiency in MuSK-MG patients.
Full Text of this Article in Japanese PDF (223K)

(CLINICA NEUROL, 52: 1306|1308, 2012)
key words: myasthenia gravis, acetylcholinesterase, collagen Q, MuSK, anti-MuSK antibody

(Received: 25-May-12)