Rheumatology Advance Access originally published online on August 18, 2009
Rheumatology 2009 48(10):1213-1217; doi:10.1093/rheumatology/kep248
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HLA–DPB1 associations differ between DRB1*03 positive anti-Jo-1 and anti-PM-Scl antibody positive idiopathic inflammatory myopathy
1Centre for Integrated Genomic Medical Research, University of Manchester, Manchester, 2The University of Manchester Rheumatic Diseases Centre, Salford Royal NHS Foundation Trust, Salford, 3Transplantation Laboratory, Manchester Royal Infirmary, Manchester, UK, 4Division of Rheumatology, University of Pittsburgh, Pittsburgh, USA, 5Rheumatology Department, Royal National Hospital for Rheumatic Diseases, Bath, 6Rheumatology Department, Royal Hospital for Sick Children, Glasgow and 7Rheumatology Unit, Institute of Child Health, UCL, London, UK.
Correspondence to: Robert G. Cooper, The University of Manchester Rheumatic Diseases Centre, Salford Royal NHS Foundation Trust, Salford M6 8HD, UK. E-mail: robert.g.cooper{at}manchester.ac.uk
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Abstract |
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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 (Pcorr) = 2 x 10–03; odds ratio (OR) 2.0; 95% CI 1.4, 2.9], PM (Pcorr = 7 x 10–03; OR 2.5; 95% CI 1.5, 4.4) and anti-Jo-1 (Pcorr = 3 x 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.
KEY WORDS: Myositis, Polymyositis, Dermatomyositis, Autoantibodies, Immunogenetics, HLA, MHC, HLA–DPB1, HLA–DRB1, Haplotype
Submitted 11 March 2009;
revised version accepted 15 July 2009.
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