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Abstract
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.
GLOSSARY
- EBV=
- Epstein-Barr virus;
- FDR=
- false discovery rate;
- ICC=
- immunocytochemistry;
- IgG=
- immunoglobulin G;
- MAG=
- myelin-associated glycoprotein;
- MBP=
- myelin basic protein;
- MOG=
- myelin oligodendrocyte glycoprotein;
- MS=
- multiple sclerosis;
- MYL5=
- myosin light chain 5;
- NIND=
- noninflammatory neurologic diseases;
- OCB=
- oligoclonal bands;
- OIND=
- other inflammatory neurologic diseases;
- RBPJ=
- recombination signal binding protein for immunoglobulin kappa J region;
- RRMS=
- relapsing-remitting multiple sclerosis;
- SPMS=
- secondary progressive multiple sclerosis
Footnotes
↵* These authors contributed equally to this work.
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Editorial, page 944
Supplemental data at www.neurology.org
- Received December 10, 2012.
- Accepted in final form May 3, 2013.
- © 2013 American Academy of Neurology
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- Epstein-Barr interference with notch intracellular messaging may result in a CADASIL like picture in Multiple Sclerosis
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