title: Antibodies specific for Epstein-Barr virus nuclear antigen-1 cross-react with human heterogeneous nuclear ribonucleoprotein L.
abstract: Epstein-Barr virus (EBV) is associated with multiple sclerosis (MS), and antibodies to the EBV nuclear antigen-1 (EBNA-1) are consistently increased in MS patients. The hypothesis of this study is that anti-EBNA-1 antibodies cross-react with a self antigen in MS patients. We affinity purified anti-EBNA-1 antibodies from human plasma, used the anti-EBNA-1 to immunoprecipitate antigens from human brain, and identified bound antigens with mass spectrometry. Anti-EBNA-1 consistently bound heterogeneous nuclear ribonucleoprotein L (HNRNPL). We expressed both the long and short isoforms of this protein, and verified with Western blots and ELISA that the long isoform cross-reacts with EBNA-1. Immunohistochemistry demonstrated that anti-EBNA-1 bound to an antigen in the nucleus of cultured rat central nervous system cells. ELISA demonstrated the presence of antibodies to HNRNPL in the plasma of both healthy controls and MS patients, but anti-HNRNPL was not increased in MS patients. We conclude that HNRNPL is an autoantigen which cross-reacts with EBNA-1. The relevance of this autoantigen to MS and other autoimmune diseases remains to be investigated.
authors.affiliation: Department of Neurology, University of Texas Health Science Center at Houston, 6431 Fannin Street, Houston, TX 77030, USA. Electronic address: john.w.lindsey@uth.tmc.edu.
authors.forename: J William
authors.initials: JW
authors.lastname: Lindsey
authors.affiliation: Department of Neurology, University of Texas Health Science Center at Houston, 6431 Fannin Street, Houston, TX 77030, USA.
authors.forename: Samantha L
authors.initials: SL
authors.lastname: deGannes
authors.affiliation: Department of Neurology, University of Texas Health Science Center at Houston, 6431 Fannin Street, Houston, TX 77030, USA.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Pate
authors.affiliation: Department of Neurology, University of Texas Health Science Center at Houston, 6431 Fannin Street, Houston, TX 77030, USA.
authors.forename: Xiurong
authors.initials: X
authors.lastname: Zhao
mesh_terms: D000328:Adult; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology; D001323:Autoantibodies; D001324:Autoantigens / Q000276:immunology; D015153:Blotting, Western; D003429:Cross Reactions / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D019309:Epstein-Barr Virus Nuclear Antigens / Q000276:immunology*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D047468:Immunoprecipitation; D013058:Mass Spectrometry; D051379:Mice; D020528:Multiple Sclerosis, Chronic Progressive / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012261:Ribonucleoproteins / Q000276:immunology*; D034664:Heterogeneous-Nuclear Ribonucleoprotein L
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D001323:Autoantibodies; D001324:Autoantigens; D019309:Epstein-Barr Virus Nuclear Antigens; D012261:Ribonucleoproteins; C400563:HNRNPL protein, human; D034664:Heterogeneous-Nuclear Ribonucleoprotein L; C417029:EBV-encoded nuclear antigen 1
keywords: Antibody cross-reactivity; Epstein-Barr virus; Molecular mimicry; Multiple sclerosis