Antibody analysis revealed association of HLA-DRB1*08:02 (pC = 0.001, OR = 2.26, 95%CI = 1.2–2.4) and HLA-DQB1*04:02 alleles (pC = 0.000001, OR = 5.3, 95%CI = 2.8–10.1) to the presence of anti-Topoisomerase I antibody in SSc patients, while HLA-DQB1*03:02 was negatively associated to the presence of this autoantibody (pC = 0.006, OR = 0.34, 95%CI = 0.15–0.71). This evidence concerns the gene HLA-DQB1 and systemic sclerosis.