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Sera were assayed by Lineblot and enzyme\u2010linked immunosorbent assay (ELISA) for autoantibodies against centromere, topoisomerase 1, RNA polymerase (POLR) 3, PM\/Scl, Th\/To, NOR90, U3 RNP, Ku, Ro52, U1RNP, and RNPC3. Logistic regression models were constructed to examine whether distinct autoantibodies associated with overall cancer at any time and cancer\u2010associated scleroderma (cancer occurring three years before and after scleroderma onset). The effects of having more than one autoantibody on cancer were further examined using random forest analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 676 cases and 687 controls were studied. After adjusting for relevant covariates, anti\u2010POLR3 (odds ratio [OR] 1.47, 95% confidence interval [CI] 1.03\u20132.11) and monospecific anti\u2010Ro52 (OR 2.19, 95% CI 1.29\u20133.74) were associated with an increased overall cancer risk, whereas anticentromere (OR 0.69, 95% CI 0.51\u20130.93) and anti\u2010U1RNP (OR 0.63, 95% CI 0.43\u20130.93) were associated with lower risk. When examining risk of cancer\u2010associated scleroderma, these immune responses remained associated with increased or decreased risk: anti\u2010POLR3 (OR 2.28, 95% CI 1.33\u20133.91), monospecific anti\u2010Ro52 (OR 2.58, 95% CI 1.05\u20136.30), anticentromere (OR 0.39, 95% CI 0.20\u20130.74), and anti\u2010U1RNP (OR 0.32, 95% CI 0.11\u20130.93). Anti\u2010Ro52 plus anti\u2010U1RNP or anti\u2010Th\/To was associated with decreased cancer risk compared with anti\u2010Ro52 alone.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These data suggest that five distinct scleroderma immune responses, alone or in combination, may be useful tools to stratify the risk of cancer for scleroderma patients. Further study examining cancer risk in autoantibody subgroups relative to the general population is warranted.<\/jats:p><jats:p><jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/art42663-toc-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec>","DOI":"10.1002\/art.42663","type":"journal-article","created":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T01:44:08Z","timestamp":1690249448000},"page":"68-77","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Distinct Scleroderma Autoantibody Profiles Stratify Patients for Cancer Risk at Scleroderma Onset and During the Disease Course"],"prefix":"10.1002","volume":"76","author":[{"given":"Ji Soo","family":"Kim","sequence":"first","affiliation":[{"name":"Johns Hopkins University  Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrianne","family":"Woods","sequence":"additional","affiliation":[{"name":"Johns Hopkins University  Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Gutierrez\u2010Alamillo","sequence":"additional","affiliation":[{"name":"Johns Hopkins University  Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maureen","family":"Laffoon","sequence":"additional","affiliation":[{"name":"University of Pittsburgh Medical Center  Pittsburgh Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fredrick M.","family":"Wigley","sequence":"additional","affiliation":[{"name":"Johns Hopkins University  Baltimore 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