Since the DRB1/B5 alleles associated with anti-topo I in various ethnic groups, DRB1*11;04 in Caucasians, DRB1*08;04/*11;01 in American Africans, DRB1*11;04/*08;02 in Hispanics, and DRB5*01;02 in Japanese, have the common amino acid sequence FLEDR at amino acid positions at 67–71 in the hypervariable β1 domain of the DRB gene, we have proposed that the DRB is the primary gene associated with anti-topo I antibody in SSc patients (Fig. 1A). This evidence concerns the gene HLA-DRB5 and systemic sclerosis.