{"doi":"10.1172/jci.insight.145217","title":"Shared recognition of citrullinated tenascin-C peptides by T and B cells in rheumatoid arthritis","abstract":"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.","journal":"JCI Insight","year":2021,"id":157110,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":51,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.952,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":663327,"name":"Anja Schwenzer","orcid":"0000-0001-6375-924X","position":1,"is_corresponding":false},{"id":496283,"name":"Alicia Wong","orcid":"0000-0002-6679-8436","position":2,"is_corresponding":false},{"id":663328,"name":"Sara Turcinov","orcid":"0000-0002-7476-1019","position":3,"is_corresponding":false},{"id":247326,"name":"Cliff Rims","orcid":"0009-0003-0342-4378","position":4,"is_corresponding":false},{"id":663329,"name":"Lorena Rodríguez-Martinez","orcid":"0000-0002-9604-6833","position":5,"is_corresponding":false},{"id":357604,"name":"David Arribas-Layton","orcid":null,"position":6,"is_corresponding":false},{"id":663330,"name":"Christina Gerstner","orcid":"0009-0003-4342-4241","position":7,"is_corresponding":false},{"id":308286,"name":"Virginia Muir","orcid":"0000-0002-6384-4572","position":8,"is_corresponding":false},{"id":663331,"name":"Kim S. Midwood","orcid":"0000-0002-8813-2977","position":9,"is_corresponding":false},{"id":28665,"name":"Vivianne Malmström","orcid":"0000-0001-9251-8082","position":10,"is_corresponding":false},{"id":108429,"name":"Eddie A. James","orcid":"0000-0002-7217-5729","position":11,"is_corresponding":false},{"id":226226,"name":"Jane H. Buckner","orcid":"0000-0002-9005-1885","position":12,"is_corresponding":false},{"id":426173,"name":"Jing Song","orcid":"0000-0003-3319-9063","position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":null,"created_at":"2026-07-18T23:44:17.471040Z","pmid":"33507879","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}