IgA autoantibodies against native myelin basic protein in a patient with MS

Myelin basic protein (MBP) is one of the most abundant proteins in the human brain. Active immunization with MBP induces experimental autoimmune encephalomyelitis, and anti-MBP antibodies have been repeatedly described in MS.1 However, its role in MS pathogenesis or prediction of disease progression is still unclear.2,3 Previous studies utilized enzyme-linked immunosorbent assay or immunoblot assays with linear epitopes of MBP, thus potentially overlooking autoantibodies that bind to MBP's natural conformation. These initial studies also included antibodies against another myelin protein, myelin oligodendrocyte glycoprotein (MOG). As happened for MBP, conflicting results stimulated the discussion of whether MOG antibodies contribute to MS pathogenesis.2,3 More recent work demonstrated that there are presumably pathogenic MOG antibodies defining the new entity of MOG antibody-associated disease;4 however, they bind to conformational MOG only. The authors are grateful to Professor Brian Popko, Department of Neurology, University of Chicago, for providing MBP knockout mouse brains.