Epitopes described in "Epitope spreading to citrullinated antigens in mouse models of autoimmune arthritis and demyelination."

Article Authors:Brian A Kidd; Peggy P Ho; Orr Sharpe; Xiaoyan Zhao; Beren H Tomooka; Jennifer L Kanter; Lawrence Steinman; William H Robinson
Article Title:Epitope spreading to citrullinated antigens in mouse models of autoimmune arthritis and demyelination.
Reference Detail
Reference ID:1013874
Abstract:INTRODUCTION: Anti-citrullinated protein antibodies have a diagnostic role in rheumatoid arthritis (RA); however, little is known about their origins and contribution to pathogenesis. Citrullination is the post-translational conversion of arginine to citrulline by peptidyl arginine deiminase, and increased citrullination of proteins is observed in the joint tissue in RA and in brain tissue in multiple sclerosis (MS). METHODS: We applied synovial and myelin protein arrays to examine epitope spreading of B cell responses to citrullinated epitopes in both the collagen-induced arthritis (CIA) model for RA and the experimental autoimmune encephalomyelitis (EAE) model for MS. Synovial and myelin protein arrays contain a spectrum of proteins and peptides, including native and citrullinated forms, representing candidate autoantigens in RA and MS, respectively. We applied these arrays to characterise the specificity of autoantibodies in serial serum samples derived from mice with acute and chronic stages of CIA and EAE. RESULTS: In samples from pre-disease CIA and acute-disease EAE, we observed autoantibody targeting of the immunising antigen and responses to a limited set of citrullinated epitopes. Over the course of diseases, the autoantibody responses expanded to target multiple citrullinated epitopes in both CIA and EAE. Using immunoblotting and mass spectrometry analysis, we identified citrullination of multiple polypeptides in CIA joint and EAE brain tissue that have not previously been described as citrullinated. CONCLUSIONS: Our results suggest that anti-citrulline antibody responses develop in the early stages of CIA and EAE, and that autoimmune inflammation results in citrullination of joint proteins in CIA and brain proteins in EAE, thereby creating neoantigens that become additional targets in epitope spreading of autoimmune responses.
Affiliations:Department of Medicine, Division of Immunology and Rheumatology, CCSR 4135, 269 Campus Dr, Stanford University School of Medicine, Stanford, CA, USA. bkidd@u.washington.edu.
Reference Type:Literature
PubMed ID:18826638
Journal:Arthritis Res Ther
Journal Volume:10
Article Pages:R119
Journal ISSN:1478-6354
Article Chemical List:Autoantibodies;Autoantigens;Epitopes, B-Lymphocyte;Citrulline
Article MeSH List:Animals; Arthritis, Experimental(immunology); Arthritis, Rheumatoid(immunology); Autoantibodies(immunology); Autoantigens(immunology; metabolism); Blotting, Western; Citrulline(immunology); Demyelinating Diseases(immunology); Encephalomyelitis, Autoimmune, Experimental(immunology); Enzyme-Linked Immunosorbent Assay; Epitopes, B-Lymphocyte(immunology); Mass Spectrometry; Mice; Protein Array Analysis
Curation Last Updated:2015-06-05 01:30:03