Reshaping the shared epitope hypothesis: HLA-associated risk for rheumatoid arthritis is encoded by amino acid substitutions at positions 67–74 of the HLA–DRB1 molecule
Version of Record online: 5 APR 2002
Copyright © 2002 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 46, Issue 4, pages 921–928, April 2002
How to Cite
de Vries, N., Tijssen, H., van Riel, P. L. C. M. and van de Putte, L. B. A. (2002), Reshaping the shared epitope hypothesis: HLA-associated risk for rheumatoid arthritis is encoded by amino acid substitutions at positions 67–74 of the HLA–DRB1 molecule. Arthritis & Rheumatism, 46: 921–928. doi: 10.1002/art.10210
- Issue online: 5 APR 2002
- Version of Record online: 5 APR 2002
- Manuscript Accepted: 5 DEC 2001
- Manuscript Received: 10 APR 2001
- Stimulation of Health Research (Stimuleringsproject gezondheidsonderzoek)
- “Het Nationaal Reumafonds” of The Netherlands (the Dutch League Against Rheumatism)
To further analyze the association of HLA–DRB1 alleles with disease susceptibility in recent-onset rheumatoid arthritis (RA).
One hundred sixty-seven Caucasian RA patients and 166 healthy controls were typed for HLA–DRB1.
The association of susceptibility to RA with the group of alleles encoding the shared epitope susceptibility sequences (SESSs) was confirmed in recent-onset RA. Among non-SESS alleles, DRB1*07, *1201, *1301, and *1501 showed significant protective effects. Even after correction for the influence of SESS alleles, significant independent protective effects of DRB1 alleles were observed. Protective alleles shared a third hypervariable region motif. Independent homozygosity effects were observed both for susceptibility and for protective alleles.
Nonsusceptibility alleles differ significantly with regard to RA risk. Protective alleles show clear homology at positions 67–74, often encoding isoleucine at position 67 or aspartic acid at position 70. Susceptibility and protective alleles both show homozygosity effects. Based on these results and on data reported in the literature, in order to incorporate the finding of differential risks among nonsusceptibility alleles, we propose to reshape the shared epitope hypothesis as follows: HLA-associated risk for RA is encoded by amino acid substitutions at positions 67–74 of the HLA–DRB1 molecule.