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Susceptibility to rheumatoid arthritis (RA) may be due to the presence of shared functional epitopes common to the HLA-DR beta chains of several RA-associated haplotypes. We have obtained direct evidence for this hypothesis by using the polymerase chain reaction and sequencing the DRB1 and DQB1 genes from RA patients. A highly conserved epitope present on DR beta chains of DR4 and DR1 haplotypes was found in 83% of 149 patients with classical or definite RA but was found in only 46% of 100 control individuals (P less than 0.0001). Two Dw subtypes of DR4 (Dw4 and Dw14) were associated with disease susceptibility but two other subtypes (Dw10 and Dw13) were not. Sequence differences between these subtypes implicate those residues around the putative antigen binding site of the DR beta molecule in the pathogenesis of RA. These data provide a basis for understanding host susceptibility to RA at a molecular level.

Original publication

DOI

10.1073/pnas.86.24.10049

Type

Journal article

Journal

Proceedings of the National Academy of Sciences of the United States of America

Publication Date

12/1989

Volume

86

Pages

10049 - 10053

Addresses

Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, United Kingdom.

Keywords

Humans, Arthritis, Rheumatoid, Disease Susceptibility, Oligonucleotide Probes, Histocompatibility Antigens Class II, HLA-DR Antigens, HLA-DR4 Antigen, Epitopes, Probability, Risk Factors, Polymerase Chain Reaction, Genes, MHC Class II, Base Sequence, Protein Conformation, Haplotypes, Alleles, Models, Molecular, Molecular Sequence Data