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

Hector Chinoy,Robert G Cooper,Chester V Oddis,Brian D Tait,Noreen Fertig,William Er Ollier,Fiona Salway,David A Isenberg,Alan J Silman,Wendy Thomson,Neil Shephard

doi:10.1186/ar1862

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 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.

Highlights

The idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of potentially serious diseases, defined by the presence of acquired muscle inflammation and weakness
Significant but weaker association was observed between DM and controls at HLA-DRB1 (p = 0.009) and DQA1 (p = 0.02), but the HLADQB1 distribution was more significant in DM (p = 0.008) than in PM (p = 0.02)
HLA-DRB1*03, DQA1*05 and DQB1*02 were removed from the data, and the overall exact tests recalculated, after which no further overall differences were detected between myositis subtype versus controls

Summary

Introduction

The idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of potentially serious diseases, defined by the presence of acquired muscle inflammation and weakness. Polymyositis (PM) and dermatomyositis (DM) are among the most frequently observed subtypes. Immunosuppressive agents and intravenous immunoglobulins can all be effective treatments, the therapeutic response to these agents is often disappointing. PM/DM patients occasionally die from their disease, or as a complication of treatment, while survivors may develop chronic disability through irreversible muscle weakness and/or interstitial lung disease (ILD). Given the relative lack of effectiveness of the available agents for PM/ DM, new and more potent therapies are clearly needed.

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