{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T13:51:42Z","timestamp":1767966702229,"version":"3.49.0"},"reference-count":60,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2009,6,29]],"date-time":"2009-06-29T00:00:00Z","timestamp":1246233600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2009,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>The association of HLA\u2013DRB1 alleles with anti\u2013citrullinated protein antibodies (ACPAs) in rheumatoid arthritis (RA) suggests the potential involvement of T lymphocytes in ACPA\u2010seropositive disease. The purpose of this study was to investigate this hypothesis by systematic histologic and molecular analyses of synovial T cells in ACPA+ versus ACPA\u2013 RA patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Synovial biopsy samples were obtained from 158 RA patients. Inflammation was determined histologically and immunohistochemically. RNA was extracted from peripheral blood mononuclear cells and synovial tissues obtained from 11 ACPA+ RA patients, 7 ACPA\u2013 RA patients, and 10 spondylarthritis (SpA) patients (arthritis controls). T lymphocyte clonality was studied by combined quantitative and qualitative T cell receptor CDR3 length distribution (LD) analysis and direct sequencing analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>ACPA+ and ACPA\u2013 RA patients were similar at both the clinical and histologic levels. At the molecular level, however, patients with ACPA+ synovitis displayed a marked elevation of qualitative CDR3 LD alterations as compared with those with ACPA\u2013 synovitis and with the SpA controls. These differences in CDR3 LD were not observed in the peripheral blood, indicating a selective recruitment and\/or local expansion of T cells in the synovial compartment. The CDR3 LD alterations reflected true monoclonal or oligoclonal expansions, as confirmed by direct sequencing of the T cell receptor. The CDR3 LD alterations in RA synovium did not correlate with B cell clonal expansions but were inversely associated with synovial lymphoid neogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The T cell repertoire is specifically restricted in RA patients with ACPA+ synovitis. Whereas the origin and role of these clonal alterations remain to be determined, our data suggest the preferential involvement of T lymphocytes in ACPA\u2010seropositive RA.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.24635","type":"journal-article","created":{"date-parts":[[2009,6,29]],"date-time":"2009-06-29T15:05:41Z","timestamp":1246287941000},"page":"1944-1956","source":"Crossref","is-referenced-by-count":64,"title":["Alterations of the synovial T cell repertoire in anti\u2013citrullinated protein antibody\u2013positive rheumatoid arthritis"],"prefix":"10.1002","volume":"60","author":[{"given":"Tineke","family":"Cantaert","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sophie","family":"Brouard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rogier M.","family":"Thurlings","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annaick","family":"Pallier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriela Franco","family":"Salinas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christophe","family":"Braud","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul L.","family":"Klarenbeek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niek","family":"de Vries","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiping","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean\u2010Paul","family":"Soulillou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul P.","family":"Tak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominique","family":"Baeten","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,6,29]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.162.1.585"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI1316"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.22206"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.26.021607.090244"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.21385"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1086\/498651"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.22704"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.21575"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2005.041079"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1080\/03009740701874444"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1423.004"},{"key":"e_1_2_6_13_2","first-page":"627","article-title":"HLA\u2010DRB1*0404 is strongly associated with high titers of anti\u2010cyclic citrullinated peptide antibodies in rheumatoid arthritis","volume":"26","author":"Charpin C","year":"2008","journal-title":"Clin Exp Rheumatol"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.22703"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.22845"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2003.017574"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2004.033571"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.11.5719"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.20012"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.22651"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.2.538"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20072051"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.21391"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.286.5441.958"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.152.10.5109"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(95)80117-0"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0298-215"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh119"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.2000.01171.x"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200110)44:10<2255::AID-ART388>3.0.CO;2-#"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.8.5057"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.21220"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1007\/s100670050134"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780310302"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780341003"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.59.12.945"},{"key":"e_1_2_6_37_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2006.062042"},{"key":"e_1_2_6_38_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.1.785"},{"key":"e_1_2_6_39_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.20476"},{"key":"e_1_2_6_40_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar1757"},{"key":"e_1_2_6_41_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.10.5088"},{"key":"e_1_2_6_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2006.06.026"},{"key":"e_1_2_6_43_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2004.00700.x"},{"key":"e_1_2_6_44_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.1.557"},{"key":"e_1_2_6_45_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.23148"},{"key":"e_1_2_6_46_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.23.10921"},{"key":"e_1_2_6_47_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118953"},{"key":"e_1_2_6_48_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780390606"},{"key":"e_1_2_6_49_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117561"},{"key":"e_1_2_6_50_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116886"},{"key":"e_1_2_6_51_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF03401692"},{"key":"e_1_2_6_52_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118220"},{"key":"e_1_2_6_53_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/6.6.897"},{"key":"e_1_2_6_54_2","doi-asserted-by":"crossref","first-page":"3538","DOI":"10.4049\/jimmunol.154.7.3538","article-title":"Analysis of clonal CD8+ T cell expansions in normal individuals and patients with rheumatoid arthritis","volume":"154","author":"Fitzgerald JE","year":"1995","journal-title":"J Immunol"},{"key":"e_1_2_6_55_2","doi-asserted-by":"crossref","first-page":"4428","DOI":"10.4049\/jimmunol.161.8.4428","article-title":"Selective accumulation of related CD4+ T cell clones in the synovial fluid of patients with rheumatoid arthritis","volume":"161","author":"Striebich CC","year":"1998","journal-title":"J Immunol"},{"key":"e_1_2_6_56_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780390312"},{"key":"e_1_2_6_57_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117624"},{"key":"e_1_2_6_58_2","doi-asserted-by":"publisher","DOI":"10.3109\/08830189809054410"},{"key":"e_1_2_6_59_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780380912"},{"key":"e_1_2_6_60_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0000055"},{"key":"e_1_2_6_61_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.23505"}],"container-title":["Arthritis &amp; Rheumatism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.24635","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.24635","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T06:39:48Z","timestamp":1698734388000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/art.24635"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,6,29]]},"references-count":60,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2009,7]]}},"alternative-id":["10.1002\/art.24635"],"URL":"https:\/\/doi.org\/10.1002\/art.24635","archive":["Portico"],"relation":{},"ISSN":["0004-3591","1529-0131"],"issn-type":[{"value":"0004-3591","type":"print"},{"value":"1529-0131","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,6,29]]}}}