To investigate the effect of ethnicity on clinical and serologic expression in patients with systemic sclerosis (SSc) and anti–DNA topoisomerase I (anti–topo I) antibody.

Clinical and serologic features, as well as HLA class II allele frequencies, were compared among 47 North American white, 15 North American black, 43 Japanese, and 12 Choctaw Native American SSc patients with anti–topo I antibody.

The frequency of progressive pulmonary interstitial fibrosis was lower, and cumulative survival rates were better in white compared with black and Japanese patients. Sera of white and black patients frequently recognized the portion adjacent to the carboxyl terminus of topo I, sera of Japanese patients preferentially recognized the portion adjacent to the amino terminus of topo I, and sera of Choctaw patients recognized both portions of topo I. Anti–RNA polymerase II and anti‐SSA/Ro antibodies were present together with anti–topo I antibody more frequently in sera of Japanese patients than in sera of white patients. The HLA–DRB1 alleles associated with anti–topo I antibody differed; i.e., DRB1*1101–*1104 in whites and blacks, DRB1*1502 in Japanese, and DRB1*1602 in Choctaws. Multivariate analysis showed that ethnic background was an independent determinant affecting development of severe lung disease as well as survival.

Clinical and serologic features in SSc patients were strongly influenced by ethnic background. The variability of disease expression in the 4 ethnic groups suggests that multiple factors linked to ethnicity, including genetic and environmental factors, modulate clinical manifestations, disease course, and autoantibody status in SSc.