HLA-DPB1 associations differ between DRB1*03 positive anti-Jo-1 and anti-PM-Scl antibody positive idiopathic inflammatory myopathy

Abstract

Objective. The HLA 8.1 ancestral haplotype (HLA-B*08/DRB1*03/DQA1*05/DQB1*02) is associated with adult/juvenile idiopathic inflammatory myopathy (IIM), but confers a greater strength of association in patients possessing anti-Jo-1 or anti-PM-Scl antibodies. The HLA–DPB1 gene is centromeric to other HLA class II loci and separated by a recombination hotspot. We investigated whether HLA–DPB1 associations differ between anti-Jo-1 and anti-PM-Scl antibody-positive IIM cases. Methods. Two hundred and thirty-three adult IIM patients (73% females, 49.4 ± 13.6 years) with PM (n = 89), DM (n = 88) and myositis associated with another CTD (n = 55) and 85 juvenile DM patients (75% females, 6.2 ± 3.6 years) were compared with 678 UK Caucasian controls. Patients/controls were genotyped for HLA–DPB1 and DRB1 alleles. Myositis-specific and associated antibodies were identified in cases using immunoprecipitation. Results. HLA–DPB1*0101 was associated with IIM overall [22 vs 13% controls, corrected probability (P_corr) = 2 × 10⁻⁰³; odds ratio (OR) 2.0; 95% CI 1.4, 2.9], PM (P_corr = 7 × 10⁻⁰³; OR 2.5; 95% CI 1.5, 4.4) and anti-Jo-1 (P_corr = 3 × 10⁻⁵; OR 4.1; 95% CI 2.1, 7.8). No significant DPB1*0101 difference was present between anti-PM-Scl cases and controls. The HLA–DPB1*0101 association in IIM overall cases was dependent on the presence of DRB1*03. A number of HLA–DRB1*03/DPB1 haplotypes were identified, but only DRB1*03/DPB1*0101 was associated with anti-Jo-1 antibody-positive cases. Conclusions. The HLA–DRB1*03/DPB1*0101 haplotype is a risk factor for anti-Jo-1 antibody-positive IIM. Thus, although DRB1*03 is strongly associated with possession of either anti-Jo-1 or anti-PM-Scl, differing antibody associations are observed at the HLA–DPB1 locus.