{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T17:25:14Z","timestamp":1788024314039,"version":"build-2784847793"},"reference-count":18,"publisher":"FapUNIFESP (SciELO)","issue":"8","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Rev. Assoc. Med. Bras."],"abstract":"<jats:p>SUMMARY  OBJECTIVE: Juvenile idiopathic arthritis is the most common chronic rheumatic disease of autoimmune origin in childhood. While altered DNA methylation has been associated with adult autoimmune rheumatic diseases, studies on juvenile idiopathic arthritis remain limited. This study evaluated levels of 5-methylcytosine and 5-hydroxymethylcytosine, important epigenetic biomarkers, in juvenile idiopathic arthritis and its subtypes.  METHODS: This single-center cross-sectional study included patients diagnosed with juvenile idiopathic arthritis aged 1 month to 18 years. Children with systemic or autoimmune diseases and comorbidities were excluded. The study comprised 58 juvenile idiopathic arthritis patients and 35 age-gender-matched healthy controls presenting with non-rheumatological complaints. Demographic and clinical characteristics, including juvenile idiopathic arthritis subtypes, were recorded. The 5-methylcytosine and 5-hydroxymethylcytosine levels were assessed quantitatively using an enzyme-linked immunosorbent assay kit. The relationships between 5-methylcytosine and 5-hydroxymethylcytosine and juvenile idiopathic arthritis and its subtypes were evaluated statistically.  RESULTS: The 5-hydroxymethylcytosine level was significantly higher, whereas the 5-methylcytosine and 5-methylcytosine\/5-hydroxymethylcytosine ratios were significantly lower in the patient group than in the control group. No significant differences between different juvenile idiopathic arthritis subtypes and disease activity status were found in 5-hydroxymethylcytosine and 5-methylcytosine levels or 5-methylcytosine\/5-hydroxymethylcytosine ratios (p&gt;0.05). The 5-methylcytosine\/5-hydroxymethylcytosine ratio, with an optimal cut-off value of \u226428.05, demonstrated a sensitivity of 70.69% and a specificity of 77.14% in distinguishing juvenile idiopathic arthritis patients from controls (p&lt;0.001).  CONCLUSION: 5-Hydroxymethylcytosine and 5-methylcytosine can be potential biomarkers for juvenile idiopathic arthritis and its subtypes, indicating their roles in juvenile idiopathic arthritis development regarding molecular mechanisms and novel therapeutic approaches.<\/jats:p>","DOI":"10.1590\/1806-9282.20250181","type":"journal-article","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T15:04:51Z","timestamp":1758294291000},"source":"Crossref","is-referenced-by-count":1,"title":["Evaluation of 5-methylcytosine and 5-hydroxymethylcytosine levels in juvenile idiopathic arthritis and its types"],"prefix":"10.1590","volume":"71","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9082-6804","authenticated-orcid":false,"given":"Seyda","family":"Dogantan","sequence":"first","affiliation":[{"name":"Ba\u015fak\u015fehir \u00c7am and Sakura City Hospital,  Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8095-2017","authenticated-orcid":false,"given":"Burcu Bozkaya","family":"Y\u00fccel","sequence":"additional","affiliation":[{"name":"Samsun Education and Research Hospital,  Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2378-1535","authenticated-orcid":false,"given":"Sevde Hasano\u011flu","family":"Sayin","sequence":"additional","affiliation":[{"name":"Bezmialem Vak\u0131f University,  Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3400-1514","authenticated-orcid":false,"given":"Sema Nur","family":"Taskin","sequence":"additional","affiliation":[{"name":"Eskisehir State Hospital,  Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1338-0087","authenticated-orcid":false,"given":"Yasemin","family":"Oyaci","sequence":"additional","affiliation":[{"name":"Istanbul University,  Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1272-5845","authenticated-orcid":false,"given":"Sacide","family":"Pehlivan","sequence":"additional","affiliation":[{"name":"Istanbul University,  Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"530","published-online":{"date-parts":[[2025]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.jaut.2017.09.010","article-title":"The DNA methylation landscape of CD4+ T cells in oligoarticular juvenile idiopathic arthritis","volume":"86","author":"Chavez-Valencia RA","year":"2018","journal-title":"J Autoimmun"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/1546-0096-6-11","article-title":"A comprehensive review of the genetics of juvenile idiopathic arthritis","volume":"6","author":"Prahalad S","year":"2008","journal-title":"Pediatr Rheumatol Online J"},{"key":"ref3","first-page":"43","article-title":"Epigenetics and cellular metabolism","volume":"8","author":"Xu W","year":"2016","journal-title":"Genet Epigenet"},{"issue":"6","key":"ref4","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1038\/nrc3728","article-title":"Clinical implications of (epi)genetic changes in HPV-induced cervical precancerous lesions","volume":"14","author":"Steenbergen RD","year":"2014","journal-title":"Nat Rev Cancer"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.mrrev.2014.09.003","article-title":"5-Hydroxymethylcytosine and disease","volume":"762","author":"Wang J","year":"2014","journal-title":"Mutat Res Rev Mutat 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and CXCR3 to the inflamed joints of children with juvenile idiopathic arthritis","volume":"43","author":"Wedderburn LR","year":"2000","journal-title":"Arthritis Rheum"},{"issue":"3","key":"ref10","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1007\/s12016-015-8493-8","article-title":"Environmental basis of autoimmunity","volume":"50","author":"Floreani A","year":"2016","journal-title":"Clin Rev Allergy Immunol"},{"issue":"1","key":"ref11","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1007\/s12016-009-8168-4","article-title":"Epigenetics lessons from twins: prospects for autoimmune disease","volume":"39","author":"Ballestar E","year":"2010","journal-title":"Clin Rev Allergy Immunol"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.conb.2019.09.012","article-title":"Transgenerational epigenetic inheritance: from phenomena to molecular mechanisms","volume":"59","author":"Liberman N","year":"2019","journal-title":"Curr Opin 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culprit in systemic lupus erythematosus: abnormal epigenetic regulation","volume":"16","author":"Wu H","year":"2015","journal-title":"Int J Mol Sci"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.jaut.2013.01.005","article-title":"Impaired DNA methylation and its mechanisms in CD4(+)T cells of systemic lupus erythematosus","volume":"41","author":"Zhang Y","year":"2013","journal-title":"J Autoimmun"},{"issue":"5","key":"ref18","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1080\/03009740902758875","article-title":"Abnormal DNA methylation in CD4+ T cells from patients with systemic lupus erythematosus, systemic sclerosis, and dermatomyositis","volume":"38","author":"Lei W","year":"2009","journal-title":"Scand J Rheumatol"}],"container-title":["Revista da Associa\u00e7\u00e3o M\u00e9dica 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