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The detection of more than one SSc-Abs in SSc patients is rare and only few data about these patients\u2019 clinical phenotype is available. The aim of our study was to evaluate the frequency and the disease\u2019s features associated with the presence of\u2009&gt;\u20091 SSc-Abs positivity in a large cohort of SSc patients. The autoantibody profiles of 2799 SSc patients from February 2001 to June 2017 were retrospectively reviewed. Patients with\u2009&gt;\u20091 SSc-Abs were identified. Clinical features were collected and compared to a large historical cohort of SSc patients with single SSc-Ab positivity. SSc patients were excluded if previously treated with rituximab, intravenous immunoglobulins or stem cell transplantation. Non-parametric tests were used for statistical analysis. Nearly 5% of SSc patients from our cohort had\u2009\u2265\u20092 autoantibody positivity, and 2.3% (n\u2009=\u200972) had\u2009\u2265\u20092 SSc-Abs positivity. Th\ne most common combination was U1RNP and ATA (35%). These patients were younger than patients with single autoantibody positivity and showed more commonly a diffuse cutaneous SSc form. They also had higher rates of overlap features compared to ATA patients. Other combinations included U1RNP and ACA (13%), ATA and ACA (7%) and U1RNP and PmScl (5%). In our study we observed that, while infrequently, SSc patients can present with a combination of two SSc-Abs and that the double positivity can influence their clinical phenotype compared to patients with single SSc-Ab positivity. The importance of re-testing SSc-Abs in patients with changing clinical phenotypes was also highlighted, as this may confer a differing risk stratification.<\/jats:p>","DOI":"10.1038\/s41598-022-15062-4","type":"journal-article","created":{"date-parts":[[2022,7,2]],"date-time":"2022-07-02T06:02:55Z","timestamp":1656741775000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Combinations of scleroderma hallmark autoantibodies associate with distinct clinical phenotypes"],"prefix":"10.1038","volume":"12","author":[{"given":"Kristina E. 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