{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T20:08:24Z","timestamp":1772827704304,"version":"3.50.1"},"reference-count":25,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2019,8,1]],"date-time":"2019-08-01T00:00:00Z","timestamp":1564617600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01 AR073208"],"award-info":[{"award-number":["1R01 AR073208"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K23 AR061439"],"award-info":[{"award-number":["K23 AR061439"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30\u2010AR070254"],"award-info":[{"award-number":["P30\u2010AR070254"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 GM12104"],"award-info":[{"award-number":["R01 GM12104"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001845","name":"Scleroderma Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001845","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis & Rheumatology"],"published-print":{"date-parts":[[2019,9]]},"abstract":"\n Objective<\/jats:title>\n \n While compelling data suggest a cancer\u2010induced autoimmunity model in scleroderma patients with anti\u2013\n RNA<\/jats:styled-content>\n polymerase\n III<\/jats:styled-content>\n large subunit (anti\u2010\n RPC<\/jats:styled-content>\n 155) antibodies, ~85% of these patients do not manifest cancer. This study was undertaken to determine whether additional autoantigens are targeted in anti\u2010\n RPC<\/jats:styled-content>\n 155\u2013positive scleroderma patients without detectable cancer.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n The study included 168 scleroderma patients with anti\u2010\n RPC<\/jats:styled-content>\n 155 antibodies (80 with a history of cancer and 88 with no cancer diagnosis after >5 years of follow\u2010up). Thirty\u2010five sera (17 from patients with cancer and 18 from patients without cancer) were randomly selected for autoantibody discovery using immunoprecipitation (\n IP<\/jats:styled-content>\n ). An ~194\u2010kd band was enriched in the subgroup without cancer; this was identified as\n RNA<\/jats:styled-content>\n polymerase I large subunit (\n RPA<\/jats:styled-content>\n 194).\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n RPA<\/jats:styled-content>\n 194 generated by in vitro transcription\/translation was used for IPs performed on the entire cohort to test whether anti\u2010\n RPA<\/jats:styled-content>\n 194 was enriched among anti\u2010\n RPC<\/jats:styled-content>\n 155\u2013positive patients without cancer. Anti\u2010\n RPA<\/jats:styled-content>\n 194 antibodies were significantly more common in the group without cancer (16 [18.2%] of 88) than in the group with cancer (3 [3.8%] of 80) (\n P<\/jats:italic>\n = 0.003). Patients with both anti\u2010\n RPA<\/jats:styled-content>\n 194 and anti\u2010\n RPC<\/jats:styled-content>\n 155 were significantly less likely to have severe gastrointestinal disease than patients with anti\u2010\n RPC<\/jats:styled-content>\n 155 only (26.3% versus 51.0%;\n P<\/jats:italic>\n = 0.043).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n Anti\u2010\n RPA<\/jats:styled-content>\n 194 antibodies are enriched in anti\u2010\n RPC<\/jats:styled-content>\n 155\u2013positive scleroderma patients without cancer. Since somatic mutations in the gene encoding\n RPC155<\/jats:italic>\n in cancer in scleroderma patients appears to play a role in immune response initiation against\n RPC<\/jats:styled-content>\n 155 in those patients, these data raise the possibility that the development of immune responses to both\n RPC<\/jats:styled-content>\n 155 and\n RPA<\/jats:styled-content>\n 194 may influence clinical cancer emergence. Further study is required to define whether different autoantibody combinations have utility as tools for cancer risk stratification in scleroderma.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/art.40893","type":"journal-article","created":{"date-parts":[[2019,3,19]],"date-time":"2019-03-19T23:44:18Z","timestamp":1553039058000},"page":"1571-1579","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Protective Effect Against Cancer of Antibodies to the Large\u00a0Subunits of Both\n RNA<\/scp>\n Polymerases I and\n III<\/scp>\n in Scleroderma"],"prefix":"10.1002","volume":"71","author":[{"given":"Ami A.","family":"Shah","sequence":"first","affiliation":[{"name":"Johns Hopkins University School of Medicine Baltimore Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marikki","family":"Laiho","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine Baltimore Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antony","family":"Rosen","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine Baltimore Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Livia","family":"Casciola\u2010Rosen","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine Baltimore Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,8]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.38928"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.27549"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar3544"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar4486"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39022"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/1346-8138.12827"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.160817"},{"key":"e_1_2_7_9_1","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1136\/annrheumdis-2018-212999","article-title":"Autoantibodies and scleroderma phenotype define subgroups at high\u2010risk and low\u2010risk for cancer","volume":"77","author":"Igusa T","year":"2018","journal-title":"Ann 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