{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T03:29:43Z","timestamp":1792553383721,"version":"4.5.0"},"reference-count":40,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,2,26]],"date-time":"2023-02-26T00:00:00Z","timestamp":1677369600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005205","name":"Janssen Research and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005205","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018163","name":"Margareta af Ugglas Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018163","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007949","name":"Swedish Rheumatism Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007949","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>CD4+ T cells are implicated in rheumatoid arthritis (RA) pathology from the strong association between RA and certain HLA class II gene variants. This study was undertaken to examine the synovial T cell receptor (TCR) repertoire, T cell phenotypes, and T cell specificities in small joints of RA patients at time of diagnosis before therapeutic intervention.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Sixteen patients, of whom 11 patients were anti\u2013citrullinated protein antibody (ACPA)\u2013positive and 5 patients were ACPA\u2013, underwent ultrasound\u2010guided synovial biopsy of a small joint (n\u00a0=\u00a013) or arthroscopic synovial biopsy of a large joint (n\u00a0=\u00a03), followed by direct sorting of single T cells for paired sequencing of the \u03b1\u03b2 TCR together with flow cytometry analysis. TCRs from expanded CD4+ T cell clones of 4 patients carrying an HLA\u2013DRB1*04:01 allele were artificially reexpressed to study antigen specificity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      T cell analysis demonstrated CD4+ dominance and the presence of peripheral helper T\u2013like cells in both patient groups. We identified &gt;4,000 unique TCR sequences, as well as 225 clonal expansions. Additionally, T cells with double \u03b1\u2010chains were a recurring feature. We identified a biased gene usage of the V\n                      <jats:sub>\u03b2<\/jats:sub>\n                      chain segment TRBV20\u20101 in CD4+ cells from ACPA+ patients. In vitro stimulation of T cell lines expressing selected TCRs with an extensive panel of citrullinated and viral peptides identified several different virus\u2010specific TCRs (e.g., human cytomegalovirus and human herpesvirus 2). Still, the majority of clones remained orphans with unknown specificity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Minimally invasive biopsies of the RA synovium allow for single\u2010cell TCR sequencing and phenotyping. Clonally expanded, viral\u2010reactive T cells account for part of the diverse CD4+ T cell repertoire. TRBV20\u20101 bias in ACPA+ patients suggests recognition of common antigens.<\/jats:p>\n                    <jats:p>\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/art42407-toc-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.42407","type":"journal-article","created":{"date-parts":[[2022,11,21]],"date-time":"2022-11-21T12:24:58Z","timestamp":1669033498000},"page":"673-684","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Diversity and Clonality of T Cell Receptor Repertoire and Antigen Specificities in Small Joints of Early Rheumatoid Arthritis"],"prefix":"10.1002","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7476-1019","authenticated-orcid":false,"given":"Sara","family":"Turcinov","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Department of Medicine Solna, Center for Molecular Medicine Karolinska University Hospital and Karolinska Institutet, and Theme of Inflammation and Ageing, Medical Unit Gastro, Derma, Rheuma, Karolinska University Hospital  Solna Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"af Klint","sequence":"additional","affiliation":[{"name":"Theme of Inflammation and Ageing, Medical Unit Gastro, Derma, Rheuma, Karolinska University Hospital  Solna Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertrand","family":"Van Schoubroeck","sequence":"additional","affiliation":[{"name":"Janssen Research and Development  Beerse 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