HLA-DPB1*0101 associations in UK Caucasian adult and juvenile idiopathic inflammatory myopathy patients.

H. Chinoy, D. Payne, K.V. Poulton, N. Fertig, Z. Betteridge, H. Gunawardena, J.E. Davidson, C.V. Oddis, L.R. Wedderburn, N.J. McHugh, WER Ollier, R.G. Cooper

Research output: Contribution to conferenceOther


Background: In the IIMs, HLA-DRB1*03 is strongly associated with the possession of anti-Jo-1 or -PM-Scl antibodies. Given the other clinical differences between these subgroups, we hypothesise that genetic differences also exist.Objectives: To investigate the HLA-DPB1 locus in adult and juvenile UK Caucasians with IIMs, and examine the relationship of DPB1 with HLA-DRB1 and myositis specific/associated antibodies (MSA/MAAs).Methods: 233 adult IIM patients (73% female, 49.4±13.6 years) with polymyositis (PM, n=89), dermatomyositis (DM, n=88) and myositis associated with another connective tissue disease (myositis/CTD-overlap, n=56) and 85 juvenile DM patients (JDM, 75% female, 6.2±3.6 years) defined with probable or definite disease according to Bohan and Peter, were compared to 678 randomly selected UK Caucasian controls. Patients and controls were genotyped at HLA-DPB1 and DRB1 using a commercially available sequence specific oligonucleotide kit. The types of detectable circulating MSA (anti-Jo-1, PL-7, PL-12, EJ, OJ, KS, Mi-2, SRP, 155/140) and MAA (U1/U3-RNP, Ku, PM-Scl) was also established.Results: HLA-DPB1*0101 was a significant risk factor in the combined IIM cases (22% vs. 13% controls, corrected probability (pcorr)=0.005, odds ratio [OR] 2.0, 95% confidence interval 1.4-2.8), also in PM (27%, pcorr=0.007, OR 2.5, 95% confidence interval 1.4-4.4) and in anti-Jo-1 antibody positive patients (n=51, 43%, pcorr=3.2 x 10-5, OR 4.1, 2.1-7.8), irrespective of clinical subtype. Linkage disequilibrium was noted between DPB1*0101 and DRB1*03 in controls (D prime=0.67). No other significant DPB1 associations were noted. Whilst HLA-DRB1*03 is known to be a strong risk factor for both anti-Jo-1 and -PM-Scl antibodies (Chinoy et al, 2006), there was no significant difference in the frequency of DPB*0101 between anti-PM-Scl (n=33, 15%) and controls (13%). After multiple corrections, no HLA-DPB1 associations were noted for DM, myositis/CTD-overlap or JDM vs. controls. In a multivariate logistic regression model, the PM and anti-Jo-1 DPB*0101 associations were both lost after adjusting for DRB1*03, which remained highly significant. No interaction was noted between these two alleles and no effect on gender was noted.Conclusion: HLA-DPB1*0101 is significantly associated with PM and anti-Jo-1 positive patients, although the association appears due to LD with DRB1*03. However, there is no significant association between anti-PM-Scl positive IIM patients and DPB*0101. This is the first data from the HLA region which appears to discriminate anti-Jo-1 from anti-PM-Scl IIM patients.References: Chinoy et al. (2006). Arthritis Res Ther, 8(1), R13.
Original languageEnglish
Pages67(Suppl II):124
Publication statusPublished - 2008
EventEULAR -
Duration: 1 Jan 1824 → …


Period1/01/24 → …


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