Rheumatology International

, Volume 32, Issue 3, pp 611–619

A three-way interplay of DR4, autoantibodies and synovitis in biopsy-proven idiopathic inflammatory myositis

Authors

    • Departments of Rheumatology and Medicine, Royal Adelaide HospitalUniversity of Adelaide
  • Sue Lester
    • Department of RheumatologyQueen Elizabeth Hospital
  • Peter Bardy
    • Australian Red Cross Blood Service
  • Philip Thompson
    • Neurology DepartmentRoyal Adelaide Hospital
  • Sally Cox
    • Departments of Rheumatology and Medicine, Royal Adelaide HospitalUniversity of Adelaide
  • Peter Blumbergs
    • Department of Neuropathology, Hanson InstituteInstitute of Medical and Veterinary Science
  • Peter Roberts-Thomson
    • SA Pathology
Original Article

DOI: 10.1007/s00296-010-1637-5

Cite this article as:
Limaye, V.S., Lester, S., Bardy, P. et al. Rheumatol Int (2012) 32: 611. doi:10.1007/s00296-010-1637-5

Abstract

The aim of this study was to determine the HLA and autoantibody associations of patients with histologically confirmed idiopathic inflammatory myositis (IIM). Serum and DNA were archived from South Australian patients with biopsy-proven dermatomyositis (DM), polymyositis (PM) and inclusion body myositis (IBM). HLA typing for Class I and II alleles was performed by serology and DNA-based technology, respectively, for 133 myositis patients and 166 Caucasian population-based controls. Myositis-specific and myositis-associated autoantibodies were detected by line immunoblot. All alleles of the 8.1AH were associated with myositis susceptibility. The B8-DR3 haplotype fragment conferred the strongest susceptibility (OR 2.9, 95% CI 1.8–4.6), and the B-DR region of other ancestral haplotypes was associated with myositis subgroups. Autoantibodies were present in 42/130 (32%) IIM patients and were more frequent in DM (11/17, 65%) than PM (23/70, 33%) or IBM (8/43, 19%), P = 0.002. Autoantibodies were associated with DRB1*03 (P = 0.0005) but also with DRB1*04 (P = 0.004). The frequency of autoantibodies in the three myositis subgroups mirrored the frequency of DR4. Polyarthralgia (±synovitis) was more common in DM/PM (30/76, 39%) than IBM (3/32, 9%), P = 0.004, and there was a strong ordinal association between the prevalence of autoantibodies and polyarthralgia ± synovitis (proportional OR = 5.5, 95% CI 2.3–13.7, P = 0.0004). The central MHC region confers the strongest susceptibility for IIM and also modulates disease phenotype. Our findings reveal a novel association of autoantibodies with DR4 and with arthralgia/synovitis in IIM and raise the possibility of a genetically (DR4) determined citrullination of myositis autoantigens expressed in muscle and synovium.

Keywords

Inflammatory myositisPolymyositisDermatomyositisInclusion body myositisAutoantibodiesHLAMuscle histology

Copyright information

© Springer-Verlag 2010