{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:05:32Z","timestamp":1790399132837,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2020,9,29]],"date-time":"2020-09-29T00:00:00Z","timestamp":1601337600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Anti\u2013topoisomerase I (anti\u2013topo I) autoantibodies in systemic sclerosis (SSc) are associated with diffuse skin involvement and interstitial lung fibrosis. Thus far, however, the relationship between anti\u2013topo I antibody response and disease course has not yet been fully evaluated. This study was undertaken to gain insight into the association between characteristics of the anti\u2013topo I antibody response and clinical disease course in SSc patients positive for anti\u2013topo I antibodies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Levels of anti\u2013topo I IgG, anti\u2013topo I IgM, and anti\u2013topo I IgA were assessed in consecutive serum samples obtained from patients at baseline who were positive for anti\u2013topo I IgG in the Leiden Combined Care In Systemic Sclerosis (CCISS) cohort. One\u2010year disease progression was defined by a relevant increase in modified Rodnan skin thickness score (MRSS), decline in pulmonary function, development of digital ulcers, renal crisis, and pulmonary hypertension, and\/or mortality. Validation was performed in SSc patients who were positive for anti\u2013topo I from the Oslo University Hospital and University Hospital Zurich.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of the 103 patients with anti\u2013topo I IgG in the CCISS cohort, clinical data were available to assess 1\u2010year disease progression in 81 patients. Of these 81 patients, 23 (28%) had disease progression. At baseline, patients with disease progression were significantly more often anti\u2013topo I IgM\u2013positive than those who did not experience disease progression (21 [91%] of 23 versus 33 [57%] of 58; <jats:italic>P<\/jats:italic> &lt; 0.01). This finding was confirmed in the independent validation samples.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In SSc patients who were anti\u2013topo I IgG\u2013positive, presence of anti\u2013topo I IgM, which might be considered as a surrogate for an ongoing autoreactive B cell immune response, is associated with disease progression.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.41403","type":"journal-article","created":{"date-parts":[[2020,6,17]],"date-time":"2020-06-17T10:00:04Z","timestamp":1592388004000},"page":"1897-1904","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Association of Anti\u2013Topoisomerase I Antibodies of the IgM Isotype With Disease Progression in Anti\u2013Topoisomerase I\u2013Positive Systemic Sclerosis"],"prefix":"10.1002","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3322-0160","authenticated-orcid":false,"given":"Maaike","family":"Boonstra","sequence":"first","affiliation":[{"name":"Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2918-7361","authenticated-orcid":false,"given":"Jaap A.","family":"Bakker","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"Grummels","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maarten K.","family":"Ninaber","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Ajmone Marsan","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corrie M.","family":"Wortel","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom W. 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