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. 2005 Apr;52(4):1063-8.
doi: 10.1002/art.20989.

New classification of HLA-DRB1 alleles supports the shared epitope hypothesis of rheumatoid arthritis susceptibility

Sophie Tezenas du Montcel  1 , Laetitia Michou, Elisabeth Petit-Teixeira, José Osorio, Isabelle Lemaire, Sandra Lasbleiz, Céline Pierlot, Patrick Quillet, Thomas Bardin, Bernard Prum, François Cornelis, Françoise Clerget-Darpoux
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Free article

New classification of HLA-DRB1 alleles supports the shared epitope hypothesis of rheumatoid arthritis susceptibility

Sophie Tezenas du Montcel et al. Arthritis Rheum. 2005 Apr.
Free article

Erratum in

  • Arthritis Rheum. 2005 Nov;52(11):3659

Abstract

Objective: The shared epitope hypothesis was formulated to explain the involvement of HLA-DRB1 in rheumatoid arthritis (RA). However, several studies, which considered only the HLA-DRB1 alleles shown to be associated with RA risk, rejected this hypothesis. In this report, we propose that a different classification of HLA-DRB1 alleles be considered, based on the amino acid sequence at position 70-74.

Methods: The fit of both HLA-DRB1 classifications was tested in 2 groups of RA patients. All subjects were recruited through the European Consortium on Rheumatoid Arthritis Families, and included 100 patients with isolated RA and 132 patients with at least 1 affected sibling.

Results: The new classification produced risk estimates that fit all of the observed data, i.e., the distribution of the HLA-DRB1 genotype in the 2 patient groups, and the distribution of parental alleles shared by affected sibpairs. The risk of developing RA under this new classification depends on whether the RAA sequence occupies position 72-74 but is modulated by the amino acid at position 71 (K confers the highest risk, R an intermediate risk, A and E a lower risk) and by the amino acid at position 70 (Q or R confers a higher risk than D).

Conclusion: A new classification based on amino acid sequence allows us to show that the shared epitope RAA sequence at position 72-74 explains the data, with the risk of developing RA modulated by the amino acids at positions 70 and 71.

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