MuSK autoantibodies in myasthenia gravis detected by cell based assay — A multinational study

•We screened 904 MG sera from 13 countries using a CBA for MuSK antibodies.•MuSK Abs were detected by CBA in 83/633 (13%) AChR/MuSK/LRP4 Ab-negative patients.•16% of triple-seronegative MG patients with purely ocular MG were positive for MuSK Abs.•The MuSK antibodies positive only by CBA mostly belong to the IgM class.

Seronegative myasthenia gravis (MG) presents a serious gap in MG diagnosis and understanding. We applied a cell based assay (CBA) for the detection of muscle specific kinase (MuSK) antibodies undetectable by radioimmunoassay. We tested 633 triple-seronegative MG patients' sera from 13 countries, detecting 13% as positive. MuSK antibodies were found, at significantly lower frequencies, in 1.9% of healthy controls and 5.1% of other neuroimmune disease patients, including multiple sclerosis and neuromyelitis optica. The clinical data of the newly diagnosed MuSK-MG patients are presented. 27% of ocular seronegative patients were MuSK antibody positive. Moreover, 23% had thymic hyperplasia suggesting that thymic abnormalities are more common than believed.