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J Immunol. 2019 Apr 15;202(8):2210-2219. doi: 10.4049/jimmunol.1801295. Epub 2019 Mar 1.

Autoantibodies against Neurologic Antigens in Nonneurologic Autoimmunity.

Author information

1
Department of Neurology, Yale School of Medicine, New Haven, CT 06511.
2
Department of Immunobiology, Yale School of Medicine, New Haven, CT 06511.
3
Oxford Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX1 2JD, United Kingdom.
4
Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104.
5
Oklahoma Clinical and Translational Science Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104.
6
Department of Medicine, University of Colorado School of Medicine, Aurora, CO 80045; and.
7
Translational Research Program, Benaroya Research Institute at Virginia Mason, Seattle, WA 98101.
8
Department of Neurology, Yale School of Medicine, New Haven, CT 06511; kevin.oconnor@yale.edu david.hafler@yale.edu.

Abstract

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.

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