Analysis of HLA-DRB1 polymorphisms in Japanese patients with primary biliary cirrhosis (PBC): The HLA-DRB1polymorphism determines the relative risk of antinuclear antibodies for disease progression in PBC

Aims: Anti-gp210 and anti-centromere antibodies are different risk factors for the progression of primary biliary cirrhosis (PBC). However, the association of human leukocyte antigen (HLA) polymorphisms with these risk factors is unknown. Methods: We determined the HLA-DRB1 genotype in 334 Japanese PBC patients and studied their serum antibodies to gp210 and centromere during the 1-452-month observation period. Results: Anti-gp210 (odds ratio [OR] 46.56, 95% confidence interval [CI], 9.20-850.1) and anti-centromere antibodies (OR, 2.36, 95% CI, 1.28-4.35) were significant risk factors for jaundice- and nonjaundice-type progression, respectively. HLA-DRB1* 0405 and * 0803 predisposed patients to anti-gp210 (OR, 1.61, 95% CI, 1.08-2.39) and anti-centromere (OR, 2.30, 95% CI, 1.41-3.73) antibody production, respectively. HLA-DRB1* 1502 and * 0901 patients were predisposed to nonjaundice-type progression (OR, 1.98, 95% CI, 1.13-3.40 and OR, 1.78, 95% CI, 1.02-3.03), while HLA-DRB1* 0803 and * 0405 patients were predisposed to disease development (OR, 2.24, 95% CI, 1.48-3.41 and OR, 1.53, 95% CI, 1.11-2.11, respectively). Stratifying patients by HLA-DRB1 alleles revealed that anti-gp210 antibodies was a strong risk factor, regardless of the HLA-DRB1 alleles for jaundice-type progression, while anti-centromere antibodies was a significant risk factor for nonjaundice-type progression in patients with HLA-DRB1* 0405 (OR, 6.89, 95% CI, 2.18-26.56) and -DRB1*0803 (OR, 5.42, 95% CI, 1.47-24.62) but not other HLA-DRB1 alleles. Conclusions: HLA-DRB1 polymorphisms are significantly associated with not only disease development and progression but also antinuclear antibody production and the determination of the relative risk of antinuclear antibodies that contribute to PBC disease progression.