Volume 5 Supplement 3

3rd World Congress of the Global Arthritis Research Network (GARN): International Arthritis Summit

Open Access

Evidence for functional variation of the death receptor 3 gene predisposing rheumatoid arthritis

  • S Shiozawa1,
  • K Komai1,
  • K Osaka1,
  • Y Miura1,
  • A Hashiramoto1 and
  • K Shiozawa2
Arthritis Res Ther20035(Suppl 3):115

https://doi.org/10.1186/ar916

Published: 12 September 2003

Apoptosis of the cell is important for the pathogenesis of autoimmune diseases. We identified the death receptor 3 (DR3) gene, a family of apoptosis-inducing Fas gene6, containing four single nucleotide polymorphisms and one locus of a 14-nucleotide deletion within exon 5 and intron 5. This haplotype resulted in insertion of a portion of intron 5 into the coding sequence or deletion of exon 6, and generated premature stop codons. The thus generated mutant DR3 lacking death domain assembled with a wild-type DR3 molecule to inhibit apoptosis, and apoptosis induction by anti-DR3 antibody was impaired in the lymphocytes of individuals with mutation. We also found that experimental collagen-induced arthritis was ameliorated by anti-DR3 antibody treatment, and the haplotype was clinically found in increased frequency in familial patients with RA and the patients who underwent joint surgery as compared with controls (P < 0.0006). We surmise that this mutation is responsible for impairment of apoptosis induction in patients with rheumatoid arthritis, which may predispose to arthritic joint destruction and autoimmunity.

Authors’ Affiliations

(1)
Department of Rheumatology, Faculty of Health Science, Kobe University School of Medicine
(2)
Department of Rheumatology, Konan Kakogawa Hospital

Copyright

© BioMed Central Ltd 2003

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