alexa HLA-DR4 subtype frequencies in rheumatoid arthritis indicate that DRB1 is the major susceptibility locus within the HLA class II region.


Journal of Clinical & Cellular Immunology

Author(s): Wordsworth BP, Lanchbury JS, Sakkas LI, Welsh KI, Panayi GS,

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Abstract 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.
This article was published in Proc Natl Acad Sci U S A and referenced in Journal of Clinical & Cellular Immunology

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