Influence of ethnic background on clinical and serologic features in patients with systemic sclerosis and anti-DNA topoisomerase I antibody

Objective. To investigate the effect of ethnicity on clinical and serologic expression in patients with systemic sclerosis (SSc) and anti-DNA topoisom erase I (anti-topo I) antibody. Methods. Clinical and serologic features, as well as HLA class II allele fr equencies, were compared among 47 North American white, 15 North American b lack, 43 Japanese, and 12 Choctaw Native American SSc patients with anti-to po I antibody. Results. The frequency of progressive pulmonary interstitial fibrosis was l ower, and cumulative survival rates were better in white compared with blac k and Japanese patients. Sera of white and black patients frequently recogn ized the portion adjacent to the carboxyl terminus of topo I, sera of Japan ese patients preferentially recognized the portion adjacent to the amino te rminus 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 toge ther 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 t hat ethnic background was an independent determinant affecting development of severe lung disease as well as survival. Conclusion. Clinical and serologic features in SSc patients were strongly i nfluenced by ethnic background. The variability of disease expression in th e 4 ethnic groups suggests that multiple factors linked to ethnicity, inclu ding genetic and environmental factors, modulate clinical manifestations, d isease course, and autoantibody status in SSc.