The aim of this study was to test whether
autoantibodies against neurologic surface Ags are found in nonneurologic
autoimmune diseases, indicating a broader loss of tolerance. Patient and matched healthy donor (HD) sera were derived from four large cohorts: 1)
rheumatoid arthritis (RA) (n = 194, HD n = 64), 2)
type 1 diabetes (T1D) (n = 200, HD n = 200), 3)
systemic lupus erythematosus (SLE) (n = 200, HD n = 67; neuro-SLE n = 49, HD n = 33), and 4) a control cohort of neurologic autoimmunity (
relapsing-remitting multiple sclerosis [MS] n = 110, HD n = 110; primary progressive MS n = 9; secondary progressive MS n = 10;
neuromyelitis optica spectrum disorders n = 15; and other
neurologic disorders n = 26). Screening of 1287 unique serum samples against four neurologic surface Ags (
myelin oligodendrocyte glycoprotein,
aquaporin 4,
acetylcholine receptor, and muscle-specific
kinase) was performed with live cell-based immunofluorescence assays using flow cytometry. Positive samples identified in the screening were further validated using
autoantibody titer quantification by serial dilutions or radioimmunoassay.
Autoantibodies against neurologic surface Ags were not observed in RA and T1D patients, whereas SLE patients harbored such
autoantibodies in rare cases (2/200, 1%). Within the CNS autoimmunity control cohort,
autoantibodies against
aquaporin 4 and high-titer Abs against
myelin oligodendrocyte glycoprotein were, as expected, specific for
neuromyelitis optica spectrum disorders. We conclude that neurologic
autoantibodies do not cross disease barriers in RA and T1D. The finding of mildly increased neurologic
autoantibodies in SLE may be consistent with a broader loss of B cell tolerance in this form of systemic autoimmunity.