{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T15:41:14Z","timestamp":1790523674379,"version":"4.1.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2015,6,1]],"date-time":"2015-06-01T00:00:00Z","timestamp":1433116800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Citrullinated peptides are major targets of disease-specific autoantibodies in rheumatoid arthritis. Currently, citrullinated peptides are used as biomarkers for diagnosing rheumatoid arthritis by measuring anti-citrullinated protein Ab (ACPA) titers in patients\u2019 sera. The accumulation of citrullinated proteins at synovial inflammation sites suggests that they are possible targets for tolerance induction. The objective of the present study was to determine whether citrullinated peptides could induce tolerance in an experimental arthritis model in rats. In view of the multiplicity of target citrullinated autoantigens described for ACPA, we generated a multiepitope citrullinated peptide (Cit-ME), derived from major prevalent citrullinated autoantigens (citrullinated filaggrin, fibrinogen, vimentin, and collagen type II), and studied its effects on arthritic rats. Adjuvant-induced arthritis was induced in Lewis rats. Beginning at day 7 after disease induction, the rats received eight s.c. injections of Cit-ME on alternate days. Differences in clinical status and modulation of T cell populations were analyzed. In adjuvant-induced arthritis rats treated with Cit-ME, disease severity was significantly reduced compared with that of untreated rats. Moreover, amelioration of disease manifestations was related to an increased regulatory T cell subset and an elevated apoptosis rate of T cells associated with reduced Th17 cells. Thus, the use of citrullinated peptides\u2013based immunotherapy may be a promising approach for tolerance induction in experimental arthritis and perhaps even in susceptible individuals that are ACPA-seropositive in human arthritis.<\/jats:p>","DOI":"10.4049\/jimmunol.1402457","type":"journal-article","created":{"date-parts":[[2015,5,12]],"date-time":"2015-05-12T02:21:36Z","timestamp":1431397296000},"page":"5674-5680","source":"Crossref","is-referenced-by-count":34,"title":["Immune Tolerance Induction with Multiepitope Peptide Derived from Citrullinated Autoantigens Attenuates Arthritis Manifestations in Adjuvant Arthritis Rats"],"prefix":"10.1093","volume":"194","author":[{"given":"Smadar","family":"Gertel","sequence":"first","affiliation":[{"name":"Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center , Tel Hashomer 52621 ,","place":["Israel"]},{"name":"Sackler Faculty of Medicine, Tel Aviv University , Tel Aviv 52621 ,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy","family":"Serre","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Mixte de Recherche 5165, Centre National de la Recherche Scientifique, 1056 INSERM, Universit\u00e9 de Toulouse III , 31062 Toulouse ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yehuda","family":"Shoenfeld","sequence":"additional","affiliation":[{"name":"Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center , Tel Hashomer 52621 ,","place":["Israel"]},{"name":"Sackler Faculty of Medicine, Tel Aviv University , Tel Aviv 52621 ,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard","family":"Amital","sequence":"additional","affiliation":[{"name":"Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center , Tel Hashomer 52621 ,","place":["Israel"]},{"name":"Sackler Faculty of Medicine, Tel Aviv University , Tel Aviv 52621 ,","place":["Israel"]},{"name":"Department of Medicine \u201cB,\u201d Sheba Medical Center , Tel Hashomer 52621 ,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,6,15]]},"reference":[{"key":"2025030706545696000_r1","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.autrev.2004.09.002","article-title":"Epidemiology of adult rheumatoid arthritis","volume":"4","author":"Alamanos","year":"2005","journal-title":"Autoimmun. 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Dis."},{"key":"2025030706545696000_r9","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1172\/JCI116713","article-title":"The cytokeratin filament-aggregating protein filaggrin is the target of the so-called \u201cantikeratin antibodies,\u201d autoantibodies specific for rheumatoid arthritis","volume":"92","author":"Simon","year":"1993","journal-title":"J. Clin. Invest."},{"key":"2025030706545696000_r10","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1186\/1479-5876-11-224","article-title":"Different amounts of protein-bound citrulline and homocitrulline in foot joint tissues of a patient with anti-citrullinated protein antibody positive erosive rheumatoid arthritis","volume":"11","author":"Turunen","year":"2013","journal-title":"J. Transl. 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