{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T21:32:01Z","timestamp":1791322321131,"version":"4.3.1"},"reference-count":63,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2015,9,16]],"date-time":"2015-09-16T00:00:00Z","timestamp":1442361600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100003141","name":"National Council of Science and Technology","doi-asserted-by":"publisher","award":["161749"],"award-info":[{"award-number":["161749"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,10,13]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Antibodies against cyclic citrullinated peptides (anti-CCP) are widely used for diagnosis of rheumatoid arthritis (RA). We performed a comparative analysis of antibodies targeting the citrullinating enzyme peptidylarginine deiminase type 4 (anti-PAD4) and mutated citrullinated vimentin (anti-MCV) with anti-CCP autoantibodies in RA patients and examined their relationships with clinical parameters, cytokine profiles and the PADI4 gene. Autoantibodies were examined by enzyme-linked immunosorbent assay (ELISA) in sera of 170 RA patients and 103 controls. Cytokine profiles were measured using a multiplex system. PADI4 polymorphisms (89G &amp;gt; A, 90T &amp;gt; C and 92G &amp;gt; C) were genotyped by polymerase chain reaction\u2013restriction fragment length polymorphism (PCR\u2013RFLP). Anti-PAD4, anti-MCV and anti-CCP autoantibodies were detected in 24, 61 and 74% of RA patients, respectively. Positive correlations were observed between anti-PAD4 and disease duration; anti-CCP and erythrocyte sedimentation rate (ESR); anti-MCV and ESR and C-reactive protein. Anti-MCV antibodies were associated with high disease activity score 28 (DAS-28) in early RA. Concentrations of T helper type 1 (Th1) [tumour necrosis factor (TNF)-\u03b1, interleukin (IL)-12, IL-2, IL-1\u03b2], Th2 (IL-4, IL-6, IL-10, IL-13) and Th17 (IL-17) cytokines were higher in RA than in controls. Th2 and, to a lesser extent, Th1-related cytokines, showed positive correlations with anti-MCV and anti-CCP. The GTG haplotype in PADI4 was associated with anti-CCP and anti-MCV, but not anti-PAD4 antibodies. In conclusion, anti-PAD4 antibodies are detected mainly in established RA, which is in contrast to the early detection of antibodies against citrullinated peptide\/proteins (ACPAs). Among autoantibodies, anti-MCV appear to perform better as markers of disease activity. Furthermore, anti-CCP and anti-MCV are associated genetically with the citrullinating enzyme PAD4 and are related strongly to Th1 and Th2 cytokines, suggesting a feed-forward loop between cytokines and ACPA production.<\/jats:p>","DOI":"10.1111\/cei.12677","type":"journal-article","created":{"date-parts":[[2015,7,6]],"date-time":"2015-07-06T23:17:22Z","timestamp":1436224642000},"page":"119-131","source":"Crossref","is-referenced-by-count":57,"title":["Comparative analysis of autoantibodies targeting peptidylarginine deiminase type 4, mutated citrullinated vimentin and cyclic citrullinated peptides in rheumatoid arthritis: associations with cytokine profiles, clinical and genetic features"],"prefix":"10.1093","volume":"182","author":[{"given":"Z","family":"Reyes-Castillo","sequence":"first","affiliation":[{"name":"Research Institute in Biomedical Sciences, Department of Medical Clinics, CUCS, Universidad De Guadalajara, Guadalajara, Jalisco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C A","family":"Palafox-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Research Institute in Biomedical Sciences, Department of Medical Clinics, CUCS, Universidad De Guadalajara, Guadalajara, Jalisco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I","family":"Parra-Rojas","sequence":"additional","affiliation":[{"name":"Academic Department of Chemistry and Biologic Sciences, Universidad Autonoma De Guerrero, Chilpancingo, Guerrero"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G E","family":"Mart\u00ednez-Bonilla","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Hospital Civil De Guadalajara \u2018Fray Antonio Alcalde\u2019, Guadalajara, Jalisco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"del Toro-Arreola","sequence":"additional","affiliation":[{"name":"Institute of Chronic and Degenerative Diseases, Department of Molecular Biology and Genomics, CUCS, Universidad De Guadalajara, Guadalajara, Jalisco, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M G","family":"Ram\u00edrez-Due\u00f1as","sequence":"additional","affiliation":[{"name":"Research Institute in Biomedical Sciences, Department of Medical Clinics, CUCS, Universidad De Guadalajara, Guadalajara, Jalisco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Ocampo-Bermudes","sequence":"additional","affiliation":[{"name":"Research Institute in Biomedical Sciences, Department of Medical Clinics, CUCS, Universidad De Guadalajara, Guadalajara, Jalisco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 F","family":"Mu\u00f1oz-Valle","sequence":"additional","affiliation":[{"name":"Research Institute in Biomedical Sciences, Department of Medical Clinics, CUCS, Universidad De Guadalajara, Guadalajara, Jalisco"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,9,16]]},"reference":[{"key":"2021122010191051100_cei12677-bib-0001","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.1056\/NEJMra1004965","article-title":"The pathogenesis of rheumatoid arthritis","volume":"365","author":"McInnes","year":"2011","journal-title":"N Engl J Med"},{"key":"2021122010191051100_cei12677-bib-0002","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1038\/nrrheum.2012.134","article-title":"Pre-rheumatoid arthritis: predisposition and transition to clinical synovitis","volume":"8","author":"Arend","year":"2012","journal-title":"Nat Rev Rheumatol"},{"key":"2021122010191051100_cei12677-bib-0003","doi-asserted-by":"crossref","first-page":"R784","DOI":"10.1186\/ar1733","article-title":"Early rheumatoid arthritis is characterized by a distinct and transient synovial fluid cytokine profile of T cell and stromal cell 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