{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T03:08:34Z","timestamp":1787972914807,"version":"build-2784847793"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T00:00:00Z","timestamp":1755475200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["No.\u202f2022YFC2504601"],"award-info":[{"award-number":["No.\u202f2022YFC2504601"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>This study aimed to evaluate the clinical and immunological significance of anti-Ro52\/TRIM21 and anti-Ro60\/SSA antibodies in rheumatoid arthritis (RA), particularly the association of dual antibody positivity with disease severity, systemic manifestations, and therapeutic resistance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted a cohort study involving 670 RA patients, stratified into four groups according to anti-Ro52 and anti-Ro60 antibody status: Ro52+\/Ro60+, Ro52+\/Ro60\u2212, Ro52\u2212\/Ro60+, and Ro52\u2212\/Ro60\u2212. Clinical characteristics, disease activity scores (DAS28-ESR, DAS28-CRP), systemic complications, and treatment responses were compared among groups. Multivariate logistic regression models identified independent predictors of difficult-to-treat RA (D2T-RA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Patients with dual Ro52+\/Ro60+ positivity exhibited significantly higher disease activity (median DAS28-ESR: 4.97 <jats:italic>vs<\/jats:italic>. 4.39, p = 0.002), worse functional status (median HAQ-DI: 0.88 <jats:italic>vs<\/jats:italic>. 0.63, p = 0.001), and increased systemic complications, notably interstitial lung disease (OR = 4.14, 95% CI: 1.71\u201310.68, p = 0.002) and hematologic involvement (OR = 2.50, 95% CI: 1.02\u20136.19, p = 0.044), compared to antibody-negative patients. Dual antibody positivity independently predicted an increased risk of developing D2T-RA (OR = 4.05, 95% CI: 1.58\u201311.09, p = 0.004). Conversely, patients with isolated Ro60 positivity exhibited lower IgG levels, fewer systemic complications, and reduced reliance on biological therapies, indicating a less severe disease phenotype.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Anti-Ro antibody subtyping effectively identifies distinct clinical and immunological RA subgroups. Patients with isolated Ro60 antibody positivity display a relatively less severe clinical profile compared to those with dual antibody positivity, highlighting the importance of specific antibody profiles in guiding personalized clinical management and therapeutic decision-making.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1661334","type":"journal-article","created":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T05:29:10Z","timestamp":1755494950000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Dual vs. isolated anti-Ro antibody positivity in rheumatoid arthritis"],"prefix":"10.3389","volume":"16","author":[{"given":"Yan","family":"Ma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoyu","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianqian","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liangjing","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/606195","article-title":"Clinical and pathological roles of Ro\/SSA autoantibody system","volume":"2012","author":"Yoshimi","year":"2012","journal-title":"Clin Dev Immunol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2021.102724","article-title":"Anti-Ro60 and anti-Ro52\/TRIM21: Two distinct autoantibodies in systemic autoimmune diseases","volume":"124","author":"Lee","year":"2021","journal-title":"J Autoimmun"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114968","article-title":"Protein heterogeneity in the human Ro\/SSA ribonucleoproteins. 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