{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T12:30:52Z","timestamp":1790771452137,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2021,11,2]],"date-time":"2021-11-02T00:00:00Z","timestamp":1635811200000},"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":[[2021,12]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Little is known on the disease course of very early systemic sclerosis (SSc). Among the information yet to be elucidated is whether anticentromere antibody (ACA) isotype levels can serve as biomarkers for future SSc development and for organ involvement. This study was undertaken to evaluate whether IgG, IgM, and IgA ACA levels in IgG ACA\u2013positive patients are associated with disease severity and\/or progression from very early SSc to definite SSc.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>IgG ACA\u2013positive patients from 5 different cohorts who had very early SSc or SSc fulfilling the American College of Rheumatology (ACR)\/European Alliance of Associations for Rheumatology (EULAR) 2013 criteria were included. A diagnosis of very early SSc was based on the presence of IgG ACAs and Raynaud\u2019s phenomenon, and\/or puffy fingers and\/or abnormal nailfold capillaroscopy, but not fulfilling the ACR\/EULAR 2013 criteria for SSc. Multivariable regression analyses were performed to determine the association between baseline ACA isotype levels and progression to definite SSc with organ involvement.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Six hundred twenty\u2010five IgG ACA\u2013positive patients were included, of whom 138 (22%) fulfilled the criteria for very early SSc and 487 (78%) had definite SSc. Levels of IgG ACAs (odds ratio 2.5 [95% confidence interval 1.8\u20133.7]) and IgM ACAs (odds ratio 1.8 [95% confidence interval 1.3\u20132.3]) were significantly higher in patients with definite SSc. Of 115 patients with very early SSc with follow\u2010up, progression to definite SSc occurred within 5 years in 48 (42%). Progression to definite SSc was associated with higher IgG ACA levels at baseline (odds ratio 4.3 [95% confidence interval 1.7\u201310.7]).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>ACA isotype levels may serve as biomarkers to identify patients with very early SSc who are at risk for disease progression to definite SSc.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.41814","type":"journal-article","created":{"date-parts":[[2021,5,27]],"date-time":"2021-05-27T07:46:44Z","timestamp":1622101604000},"page":"2338-2347","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Anticentromere Antibody Levels and Isotypes and the Development of Systemic Sclerosis"],"prefix":"10.1002","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4228-012X","authenticated-orcid":false,"given":"Nina M.","family":"van Leeuwen","sequence":"first","affiliation":[{"name":"Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3322-0160","authenticated-orcid":false,"given":"Maaike","family":"Boonstra","sequence":"additional","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":"Suzana","family":"Jordan","sequence":"additional","affiliation":[{"name":"University Hospital Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0328-7062","authenticated-orcid":false,"given":"Sophie","family":"Liem","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2413-1959","authenticated-orcid":false,"given":"Oliver","family":"Distler","sequence":"additional","affiliation":[{"name":"University Hospital Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna\u2010Maria","family":"Hoffmann\u2010Vold","sequence":"additional","affiliation":[{"name":"Oslo University Hospital and Rikshospitalet  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4125-7163","authenticated-orcid":false,"given":"Karin","family":"Melsens","sequence":"additional","affiliation":[{"name":"Ghent University Ghent University Hospital, and VIB\u2010UGent Center for Inflammation Research  Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Smith","sequence":"additional","affiliation":[{"name":"Ghent University Ghent University Hospital, and VIB\u2010UGent Center for Inflammation Research  Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie\u2010Elise","family":"Truchetet","sequence":"additional","affiliation":[{"name":"Bordeaux University Hospital  Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5700-5617","authenticated-orcid":false,"given":"Hans U.","family":"Scherer","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9","family":"Toes","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom W. 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