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Protein array-based profiling of CSF identifies RBPJ as an autoantigen in multiple sclerosis
Luis Querol1, Pamela L Clark, Mary A Bailey
1From the Department of Neurology (L.Q., P.L.C., M.A.B., C.C., D.A.H., J.-Y.L., K.C.O.), Human and Translational Immunology Program (D.A.H., K.C.O.), Department of Genetics (C.C.), Department of Pathology (S.H.K., G.Y.), and Department of Immunobiology (D.A.H.), Yale School of Medicine, New Haven, CT; Neuromuscular Diseases Unit (L.Q.), Hospital de la Santa Creu i Sant Pau, Universitat Autónoma de Barcelona, Spain; Medical and Population Genetics (C.C.), Broad Institute of MIT and Harvard, Cambridge, MA; Department of Neurology (A.H.C.), Washington University School of Medicine, St. Louis, MO; Interdepartmental Program in Computational Biology and Bioinformatics (S.H.K.), Yale University, New Haven, CT; and Department of Neurology (S.N.W.), Harvard Medical School and Brigham and Women's Hospital, Boston, MA. Simon N. Willis is currently affiliated with the Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
Researchers identified novel autoantibodies against recombination signal binding protein for immunoglobulin kappa J region (RBPJ) in the cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients. This discovery highlights RBPJ as a potential MS autoantigen specific to the central nervous system.
Area of Science:
- Neuroimmunology
- Autoimmunity
- Molecular Biology
Background:
- Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system.
- Identifying specific autoantigens in MS is crucial for understanding disease pathogenesis and developing targeted therapies.
- Cerebrospinal fluid (CSF) immunoglobulin G (IgG) profiles may offer insights into CNS-specific autoimmune responses in MS.
Purpose of the Study:
- To profile CSF-derived immunoglobulin reactivity against a comprehensive panel of antigens in MS patients.
- To identify novel disease-specific autoantigens recognized by CSF IgG in multiple sclerosis.
- To validate the diagnostic potential of identified autoantigens.
Main Methods:
- Screening of CSF from MS patients and controls against a protein array containing 9,393 proteins.
- Confirmation of candidate autoantigen reactivity using Enzyme-Linked Immunosorbent Assay (ELISA) and immunocytochemistry.
- Validation in a large cohort to assess the prevalence of autoantibodies in CSF and serum.
Main Results:
- Autoantibodies against recombination signal binding protein for immunoglobulin kappa J region (RBPJ) significantly distinguished MS patients from controls (p = 0.0052).
- ELISA confirmed a higher prevalence of anti-RBPJ autoantibodies in MS patient CSF (12.5%) compared to controls (1.6%; p = 0.02).
- This reactivity was specific to CSF, as serum anti-RBPJ autoantibodies did not differ between groups.
Conclusions:
- Recombination signal binding protein for immunoglobulin kappa J region (RBPJ) is a novel candidate autoantigen in a subset of MS patients.
- The identified autoantibodies are recognized by CSF-derived IgG, suggesting a role in CNS autoimmunity.
- RBPJ, a component of the Notch signaling pathway, represents a potential biomarker for MS.
