{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:07:50Z","timestamp":1772118470393,"version":"3.50.1"},"reference-count":31,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2019,8,22]],"date-time":"2019-08-22T00:00:00Z","timestamp":1566432000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Low T\u2010cell receptor (TCR)\/CD28 signaling lymphocytes are expanded in arthritis. We asked whether the down\u2010expression of TCR\u2010related molecules correlates with specific arthritis characteristics and if it has clinical implications. TCR\u2010ZETA, ZAP\u201070 and CD28 expression was measured by flow cytometry in synovial fluid (SF) and peripheral blood (PB)\u2010derived T cells. In PB, ZETA\u2010downregulation in CD4\n                    <jats:sup>+<\/jats:sup>\n                    CD28\n                    <jats:sup>+<\/jats:sup>\n                    and consequent CD4\n                    <jats:sup>+<\/jats:sup>\n                    <jats:italic>CD28lowZETAlow<\/jats:italic>\n                    cell expansion correlate with CRP elevation, leukocyte recruitment into SF and, primarily, disease activity (DAS). In some patients, ZETA\u2010downregulation extends to CD8\n                    <jats:sup>+<\/jats:sup>\n                    CD28null and\/or CD8\n                    <jats:sup>+<\/jats:sup>\n                    CD28\n                    <jats:sup>+<\/jats:sup>\n                    cells, and this correlates with enhanced leukocyte recruitment, multiple joint involvement, and disability index (HAQ). ZETA\u2010downregulation in CD4\n                    <jats:sup>+<\/jats:sup>\n                    CD28\n                    <jats:sup>+<\/jats:sup>\n                    may also lead to CD4\n                    <jats:sup>+<\/jats:sup>\n                    <jats:italic>\n                      CD28\n                      <jats:sup>+<\/jats:sup>\n                      ZETAnull\n                    <\/jats:italic>\n                    cell expansion, which strongly correlates with HAQ.\n                  <\/jats:p>\n                  <jats:p>\n                    In SF, ZETA\u2010downregulation in CD8\n                    <jats:sup>+<\/jats:sup>\n                    CD28null and consequent CD8\n                    <jats:sup>+<\/jats:sup>\n                    <jats:italic>CD28nullZETAlow\/null<\/jats:italic>\n                    cell expansion correlate with CRP elevation and neutrophilic influx into SF, whereas ZAP\u2010downregulation in CD8\n                    <jats:sup>+<\/jats:sup>\n                    CD28\n                    <jats:sup>+<\/jats:sup>\n                    and consequent CD8\n                    <jats:sup>+<\/jats:sup>\n                    <jats:italic>CD28lowZAPlow<\/jats:italic>\n                    cell expansion strongly correlate with HAQ and DAS.\n                  <\/jats:p>\n                  <jats:p>\n                    ZETA\u2010downregulation is preponderant in SF of seronegative arthritides, with seronegative rheumatoid arthritis showing significant down\u2010regulation in CD8\n                    <jats:sup>+<\/jats:sup>\n                    CD28null, and non\u2010rheumatoid arthritides showing significant down\u2010regulation in CD4\n                    <jats:sup>+<\/jats:sup>\n                    CD28\n                    <jats:sup>+<\/jats:sup>\n                    .\n                  <\/jats:p>\n                  <jats:p>Altogether, we identified new molecular and cellular biomarkers of arthritis\u2010related T\u2010cell inflammation, useful for assessing arthritis activity, predicting polyarticular progression and functional impairment, characterizing seronegative arthritides, and possibly tailoring immunotherapies.<\/jats:p>","DOI":"10.1002\/eji.201847849","type":"journal-article","created":{"date-parts":[[2019,8,10]],"date-time":"2019-08-10T11:43:16Z","timestamp":1565437396000},"page":"2195-2203","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Measuring the T\u2010cell down\u2010regulation of TCR\u2010zeta, ZAP\u201070 and CD28 in arthritis patients: An old tool for new biomarkers"],"prefix":"10.1002","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6971-4576","authenticated-orcid":false,"given":"Gaetano","family":"Zizzo","sequence":"first","affiliation":[{"name":"Division of Rheumatology Fondazione Policlinico Universitario A. Gemelli \u2010 Catholic University of the Sacred Heart  Rome Italy"},{"name":"Rheumatology Unit Medical Department, Vimercate Hospital  Monza e Brianza Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"De Santis","sequence":"additional","affiliation":[{"name":"Division of Rheumatology and Clinical Immunology Humanitas Research Hospital  Rozzano Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Bosello","sequence":"additional","affiliation":[{"name":"Division of Rheumatology Fondazione Policlinico Universitario A. Gemelli \u2010 Catholic University of the Sacred Heart  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Tolusso","sequence":"additional","affiliation":[{"name":"Division of Rheumatology Fondazione Policlinico Universitario A. Gemelli \u2010 Catholic University of the Sacred Heart  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"Alivernini","sequence":"additional","affiliation":[{"name":"Division of Rheumatology Fondazione Policlinico Universitario A. Gemelli \u2010 Catholic University of the Sacred Heart  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giacomo","family":"De Luca","sequence":"additional","affiliation":[{"name":"Unit of Immunology, Rheumatology, Allergy and Rare Diseases San Raffaele Scientific Institute  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisa","family":"Gremese","sequence":"additional","affiliation":[{"name":"Division of Rheumatology Fondazione Policlinico Universitario A. Gemelli \u2010 Catholic University of the Sacred Heart  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gianfranco","family":"Ferraccioli","sequence":"additional","affiliation":[{"name":"Division of Rheumatology Fondazione Policlinico Universitario A. Gemelli \u2010 Catholic University of the Sacred Heart  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,8,22]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1434"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.2000.01180.x"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-12-064170"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1102365"},{"key":"e_1_2_9_6_1","first-page":"413","article-title":"The potential role of Th17 in mediating the transition from acute to chronic autoimmune inflammation: rheumatoid arthritis as a model","volume":"11","author":"Ferraccioli G.","year":"2011","journal-title":"Discov Med"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1300634"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature02119"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0803600"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2010.10.002"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0402-379"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2005.00256.x"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.6.3231"},{"key":"e_1_2_9_14_1","first-page":"348746","article-title":"The story of CD4+ CD28\u2212 T cells revisited: solved or still ongoing?","volume":"2015","author":"Maly K.","year":"2015","journal-title":"J Immunol Res"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar386"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar2286"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar766"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780400615"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.11445"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1396.043"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000131450.66017.B3"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.12.8218"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.12.013"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.56.10.613"},{"key":"e_1_2_9_25_1","doi-asserted-by":"crossref","first-page":"6390","DOI":"10.4049\/jimmunol.161.11.6390","article-title":"The role of CD8+ CD40L+ T cells in the formation of germinal centers in rheumatoid synovitis","volume":"161","author":"Wagner U. G.","year":"1998","journal-title":"J. Immunol."},{"key":"e_1_2_9_26_1","first-page":"1128","article-title":"Analysis of Th1 and Th2 cytokines expressing CD4+ and CD8+ T cells in rheumatoid arthritis by flow cytometry","volume":"27","author":"Berner B.","year":"2000","journal-title":"J. Rheumatol."},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.2217\/imt-2018-0014"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-008-1030-x"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2015-207784"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39595"},{"key":"e_1_2_9_31_1","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1186\/s13075-017-1401-2","article-title":"High titers of both rheumatoid factor and anti\u2010CCP antibodies at baseline in patients with rheumatoid arthritis are associated with increased circulating baseline TNF level, low drug levels, and reduced clinical responses: a post hoc analysis of the RISING study","volume":"19","author":"Takeuchi T.","year":"2017","journal-title":"Arthritis Res. Ther."},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2017.09.002"}],"container-title":["European Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/eji.201847849","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/eji.201847849","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/eji.201847849","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,8]],"date-time":"2023-09-08T21:55:22Z","timestamp":1694210122000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/eji.201847849"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8,22]]},"references-count":31,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["10.1002\/eji.201847849"],"URL":"https:\/\/doi.org\/10.1002\/eji.201847849","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1002\/EJI.201847849\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.201847849\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.201847849\/v3\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.201847849\/v2\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.201847849\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.201847849\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.201847849\/v3\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.201847849\/v3\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.201847849\/v3\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.201847849\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.201847849\/v2\/review1","asserted-by":"object"}]},"ISSN":["0014-2980","1521-4141"],"issn-type":[{"value":"0014-2980","type":"print"},{"value":"1521-4141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,8,22]]},"assertion":[{"value":"2018-08-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-08-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-08-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}