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In this study, we utilized a systematic discovery process and identified 5 potentially novel citrullinated TNC (cit-TNC) T cell epitopes. CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells specific for these epitopes were elevated in the peripheral blood of subjects with RA and showed signs of activation. Cit-TNC\u2013specific T cells were also present among synovial fluid T cells and secreted IFN-\u03b3. 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\u2013reactive antibodies were prevalent among subjects with RA and positively associated with cyclic citrullinated peptide (CCP) reactivity and the HLA shared epitope. Furthermore, cit-TNC\u2013reactive 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\n                    <jats:sup>+<\/jats:sup>\n                    T cells and autoantibodies in patients with RA. Furthermore, our findings raise the possibility that coinciding epitopes recognized by both CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells and B cells have the potential to amplify autoimmunity and promote the development and progression of RA.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.145217","type":"journal-article","created":{"date-parts":[[2021,1,28]],"date-time":"2021-01-28T12:24:37Z","timestamp":1611836677000},"source":"Crossref","is-referenced-by-count":50,"title":["Shared recognition of citrullinated tenascin-C peptides by T and B cells in rheumatoid arthritis"],"prefix":"10.1172","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3319-9063","authenticated-orcid":true,"given":"Jing","family":"Song","sequence":"first","affiliation":[{"name":"Center for Translational Immunology, Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6375-924X","authenticated-orcid":true,"given":"Anja","family":"Schwenzer","sequence":"additional","affiliation":[{"name":"Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Wong","sequence":"additional","affiliation":[{"name":"Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7476-1019","authenticated-orcid":true,"given":"Sara","family":"Turcinov","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cliff","family":"Rims","sequence":"additional","affiliation":[{"name":"Center for Translational Immunology, Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorena Rodriguez","family":"Martinez","sequence":"additional","affiliation":[{"name":"Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Arribas-Layton","sequence":"additional","affiliation":[{"name":"Center for Translational Immunology, Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Gerstner","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6384-4572","authenticated-orcid":true,"given":"Virginia S.","family":"Muir","sequence":"additional","affiliation":[{"name":"Center for Systems Immunology, Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim S.","family":"Midwood","sequence":"additional","affiliation":[{"name":"Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9251-8082","authenticated-orcid":true,"given":"Vivianne","family":"Malmstr\u00f6m","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7217-5729","authenticated-orcid":true,"given":"Eddie A.","family":"James","sequence":"additional","affiliation":[{"name":"Center for Translational Immunology, Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9005-1885","authenticated-orcid":true,"given":"Jane H.","family":"Buckner","sequence":"additional","affiliation":[{"name":"Center for Translational Immunology, Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2021,3,8]]},"reference":[{"key":"B1","unstructured":"World Health Organization. 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