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One hallmark of the immunological abnormalities in systemic sclerosis is the presence of anti-nuclear antibodies, which are detected in more than 90% of patients with systemic sclerosis. Anti-centromere antibodies, anti-DNA topoisomerase I antibodies, and anti-RNA polymerase III antibodies are the predominant anti-nuclear antibodies found in systemic sclerosis patients. Other systemic sclerosis\u2013related anti-nuclear antibodies include those targeted against U3 ribonucleoprotein, Th\/To, U11\/U12 ribonucleoprotein, and eukaryotic initiation factor 2B. Anti-U1 ribonucleoprotein, anti-Ku antibodies, anti-PM\u2013Scl, and anti-RuvBL1\/2 antibodies are associated with systemic sclerosis overlap syndrome. Anti-human upstream binding factor, anti-Ro52\/TRIM21, anti-B23, and anti-centriole antibodies do not have specificity to systemic sclerosis, but are sometimes detected in sera from patients with systemic sclerosis. Identification of each systemic sclerosis\u2013related antibody is useful to diagnose and predict organ involvement, since the particular type of systemic sclerosis\u2013related antibodies is often predictive of clinical features, severity, and prognosis. The clinical phenotypes are largely influenced by ethnicity. 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