New Classification of HLA-DRB1 Alleles Supports the Shared Epitope Hypothesis of Rheumatoid Arthritis Susceptibility - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Arthritis & rheumatology Année : 2005

New Classification of HLA-DRB1 Alleles Supports the Shared Epitope Hypothesis of Rheumatoid Arthritis Susceptibility

Résumé

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. © 2005, American College of Rheumatology.

Dates et versions

hal-02084369 , version 1 (29-03-2019)

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Citer

Sophie Tézenas Du Montcel, Laëtitia Michou, Elisabeth Petit-Teixeira, José Osorio, Isabelle Lemaire, et al.. New Classification of HLA-DRB1 Alleles Supports the Shared Epitope Hypothesis of Rheumatoid Arthritis Susceptibility. Arthritis & rheumatology, 2005, 52 (4), pp.1063--1068. ⟨10.1002/art.20989⟩. ⟨hal-02084369⟩
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