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Publication Detail
In adult onset myositis, the presence of interstitial lung disease and myositis specific/associated antibodies are governed by HLA class II haplotype, rather than by myositis subtype
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Journal Article
  • Authors:
    Chinoy H, Salway F, Fertig N, Shephard N, Tait BD, Thomson W, Isenberg DA, Oddis CV, Silman AJ, Ollier WER, Cooper RG, Bernstein RM, Beynon HLC, Black CM, Borg A, Bruce IN, Bruckner FE, Butler RC, Carty JE, Clarke F, Dawes PT, Devlin JAJ, Emery P, Fordham JN, Fraser AD, Gaston JSH, George E, Griffiths B, Griffiths ID, Harrison BJ, Hay EM, Herrick AL, Hilton RC, Hilton-Jones D, Hurst NP, Isaacs JD, Jones AC, Jones AKP, Kennedy TD, Kitas GD, Klimiuk PS, Lanyon PC, Lecky BRF, Linton S, Luqmani RA, Marks JS, Martin MFR, McKenna F, McLaren J, McMahon MJ, McRorie ER, Merry PH, Nicholls A, Over KE, Packham JC, Pipitone N, Plant MJ, Pullar T, Roberts ME, Sanders P, Scott DGI, Scott DL, Sheeran TPG, Srinivasan U, Swinson DR, Teh LS, Williams BD, Winer JB
  • Publication date:
    05/12/2006
  • Journal:
    Arthritis Research and Therapy
  • Volume:
    8
  • Issue:
    1
  • Status:
    Published
  • Print ISSN:
    1478-6354
Abstract
The aim of this study was to investigate HLA class II associations in polymyositis (PM) and dermatomyositis (DM), and to determine how these associations influence clinical and serological differences. DNA samples were obtained from 225 UK Caucasian idiopathic inflammatory myopathy patients (PM = 117, DM = 108) and compared with 537 randomly selected UK Caucasian controls. All cases had also been assessed for the presence of related malignancy and interstitial lung disease (ILD), and a number of myositis-specific/myositis-associated antibodies (MSAs/MAAs). Subjects were genotyped for HLADRB1, DQA1 and DQB1. HLA-DRB1*03, DQA1*05 and DQB1*02 were associated with an increased risk for both PM and DM. The HLA-DRB1*03-DQA1*05-DQB1*02 haplotype demonstrated strong association with ILD, irrespective of myositis subtype or presence of anti-aminoacyl-transfer RNA synthetase antibodies. The HLA-DRB1*07-DQA1*02-DQB1*02 haplotype was associated with risk for anti-Mi-2 antibodies, and discriminated PM from DM (odds ratio 0.3, 95% confidence interval 0.1-0.6), even in anti-Mi-2 negative patients. Other MSA/MAAs showed specific associations with other HLA class II haplotypes, irrespective of myositis subtype. There were no genotype, haplotype or serological associations with malignancy. The HLA-DRB1*03-DQA1*05-DQB1*02 haplotype associations appear to not only govern disease susceptibility in Caucasian PM/DM patients, but also phenotypic features common to PM/DM. Though strongly associated with anti-Mi-2 antibodies, the HLA-DRB1*07-DQ A1*02-DQB1*02 haplotype shows differential associations with PM/DM disease susceptibility. In conclusion, these findings support the notion that myositis patients with differing myositis serology have different immunogenetic profiles, and that these profiles may define specific myositis subtypes. © 2005 Chinoy et al.; licensee BioMed Central Ltd.
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