Journal
NEUROLOGY
Volume 81, Issue 11, Pages 956-963Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1212/WNL.0b013e3182a43b48
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Funding
- National Institute of Neurological Disorders and Stroke/National Institutes of Health (NINDS/NIH) [R01NS024247]
- Nancy Davis Foundation for Multiple Sclerosis
- National Health and Medical Research Council of Australia
- Fondo de Investigaciones Sanitarias-Instituto de Salud Carlos III, Spain [FIS CM 09/00017]
- Manny and Rosalyn Rosenthal-Dr. John L. Trotter Chair in Neuroimmunology of the Barnes-Jewish Foundation
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Objective: To profile the reactivity of CSF-derived immunoglobulin from patients with multiple sclerosis (MS) against a large panel of antigens, to identify disease-specific reactivities. Methods: CSF from subjects with MS with elevated immunoglobulin G and CSF from control subjects presenting with other inflammatory neurologic disease were screened against a protein array consisting of 9,393 proteins. Reactivity to a candidate protein identified using these arrays was confirmed with ELISA and immunocytochemistry. Results: Autoantibodies against one protein on the array, recombination signal binding protein for immunoglobulin kappa J region (RBPJ), discriminated between patients with MS and controls (p = 0.0052). Using a large validation cohort, we found a higher prevalence of autoantibodies against RBPJ in the CSF of patients with MS (12.5%) compared with the CSF of patients with other neurologic diseases (1.6%; p = 0.02) by ELISA. This difference in reactivity was restricted to the CSF as serum reactivity against RBPJ did not differ between patients and controls. The presence of CSF autoantibodies against RBPJ was further confirmed by immunocytochemistry. Conclusions: These data indicate that RBPJ, a ubiquitous protein of the Notch signaling pathway that plays an important role in Epstein-Barr virus infection, is a novel MS autoantigen candidate that is recognized by CSF-derived immunoglobulin G in a subset of patients with MS.
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