{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T14:29:47Z","timestamp":1791815387697,"version":"4.3.4"},"reference-count":72,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T00:00:00Z","timestamp":1761264000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Systemic sclerosis (SSc) is clinically heterogeneous. Disease-specific autoantibodies\u2014anticentromere (ACA), anti\u2013topoisomerase I (ATA\/Scl-70), and anti\u2013RNA polymerase III (RNAP III)\u2014are central to classification and organ-risk prediction. Beyond prognosis, SSc-specific autoantibodies can support diagnosis as part of a composite assessment with nailfold capillaroscopy and clinical features; their contribution is reflected in the 2013 ACR\/EULAR classification criteria and can be informative in very-early or sine presentations. More broadly, these immune signatures underpin routine SSc care and underscore the immunological impacts that shape disease expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Narrative review (2000\u2013August 2025) prioritizing studies in Japanese and Western cohorts, with emphasis on assay performance and cohort comparability. We appraise line immunoassay (LIA) performance vis-\u00e0-vis immunoprecipitation (IP), and integrate ICAP-compliant ANA interpretation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>ACA aligns with lower ILD risk but higher PAH and digital vasculopathy; ATA predicts ILD onset\/progression; RNAP III marks rapid skin thickening, SRC risk, and temporally clustered malignancy; U1 RNP tracks overlap\/MCTD-like features and PAH; U3 RNP indicates diffuse disease with vasculopathy; Th\/To varies by center; PM-Scl and Ku flag overlap ILD\/myositis. A clinical-first standardized workflow\u2014ANA (ICAP) + core ELISAs (ACA, ATA, RNAP III, U1 RNP) followed by ANA-pattern\u2013guided LIA\/IP confirmation\u2014supports both care and cross-cohort comparability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Autoantibodies form a practical foundation for SSc care across regions. Standardizing the reflex layer (LIA\/IP) while leveraging established ANA and core ELISAs can reduce measurement-driven cohort differences and improve global synthesis of SSc evidence.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1691988","type":"journal-article","created":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T05:28:19Z","timestamp":1761283699000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["The clinical utility of autoantibodies in systemic sclerosis: a review with a focus on cohort differences and standardization"],"prefix":"10.3389","volume":"16","author":[{"given":"Kazuhiro","family":"Komura","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(17)30933-9","article-title":"Systemic 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