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
HLA-DRB1, 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-DQA1*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.