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

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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.

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Acknowledgments

We are grateful to South Australian Rheumatologists and Neurologists who have willingly contributed their patients to this database. This work was supported by a Royal Adelaide Hospital/Institute of Medical and Veterinary Science Clinical Project Grant.

Conflict of interest

None of the authors have any conflicts of interest.

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Authors and Affiliations

  1. Departments of Rheumatology and Medicine, Royal Adelaide Hospital, University of Adelaide, North Tce, Adelaide, SA, 5000, Australia

    Vidya S. Limaye & Sally Cox

  2. Department of Rheumatology, Queen Elizabeth Hospital, Adelaide, SA, Australia

    Sue Lester

  3. Australian Red Cross Blood Service, Adelaide, SA, Australia

    Peter Bardy

  4. Neurology Department, Royal Adelaide Hospital, Adelaide, SA, Australia

    Philip Thompson

  5. Department of Neuropathology, Hanson Institute, Institute of Medical and Veterinary Science, Adelaide, SA, Australia

    Peter Blumbergs

  6. SA Pathology, Adelaide, SA, Australia

    Peter Roberts-Thomson

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  1. Vidya S. Limaye
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Correspondence to Vidya S. Limaye.

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Limaye, V.S., Lester, S., Bardy, P. et al. A three-way interplay of DR4, autoantibodies and synovitis in biopsy-proven idiopathic inflammatory myositis. Rheumatol Int 32, 611–619 (2012). https://doi.org/10.1007/s00296-010-1637-5

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  • DOI: https://doi.org/10.1007/s00296-010-1637-5

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