Shared recognition of citrullinated tenascin-C peptides by T and B cells in rheumatoid arthritis

• Published in: JCI insight 2021-03, Vol.6 (5)
• Main Authors: Song, Jing, Schwenzer, Anja, Wong, Alicia, Turcinov, Sara, Rims, Cliff, Martinez, Lorena Rodriguez, Arribas-Layton, David, Gerstner, Christina, Muir, Virginia S, Midwood, Kim S, Malmström, Vivianne, James, Eddie A, Buckner, Jane H
• Format: Article
• Language: English
• Subjects: Arthritis, Rheumatoid - immunology; Autoimmunity; B-Lymphocytes - cytology; B-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - immunology; Epitopes, T-Lymphocyte - immunology; Humans; Immunology; Medicin och hälsovetenskap; Tenascin - immunology
• ISSN: 2379-3708; 2379-3708
• DOI: 10.1172/jci.insight.145217

Tenascin-C (TNC), an extracellular matrix protein that has proinflammatory properties, is a recently described antibody target in rheumatoid arthritis (RA). In this study, we utilized a systematic discovery process and identified 5 potentially novel citrullinated TNC (cit-TNC) T cell epitopes. CD4+ T cells specific for these epitopes were elevated in the peripheral blood of subjects with RA and showed signs of activation. Cit-TNC-specific T cells were also present among synovial fluid T cells and secreted IFN-γ. Two of these cit-TNC T cell epitopes were also recognized by antibodies within the serum and synovial fluid of individuals with RA. Detectable serum levels of cit-TNC-reactive antibodies were prevalent among subjects with RA and positively associated with cyclic citrullinated peptide (CCP) reactivity and the HLA shared epitope. Furthermore, cit-TNC-reactive antibodies were correlated with rheumatoid factor and elevated in subjects with a history of smoking. This work confirms cit-TNC as an autoantigen that is targeted by autoreactive CD4+ T cells and autoantibodies in patients with RA. Furthermore, our findings raise the possibility that coinciding epitopes recognized by both CD4+ T cells and B cells have the potential to amplify autoimmunity and promote the development and progression of RA.