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© 1991 British Society for Rheumatology

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LIMITED HETEROGENEITY OF THE HLA CLASS II CONTRIBUTION TO SUSCEPTIBILITY TO RHEUMATOID ARTHRITIS IS SUGGESTED BY POSITIVE ASSOCIATIONS WITH HLA—DR4, DR1 AND DRwlO

B. P. WORDSWORTH, J. STEDEFORD, W. M. C. ROSENBERG and J. I. BELL

Molecular Immunology Group, Institute of Molecular Medicine John Radcliffe Hospital, Oxford OX3 9DU

Correspondence to: Correspondence to Dr B. Wordsworth.

Most patients with rheumatoid arthritis (RA) exhibit an HLA class II epitope found on most DR4 and DR1 molecules. We have investigated the possibility of other associations being present in the minority of patients lacking these antigens. One hundred and eighty patients with classical or definite RA and 100 controls were assigned HLA—DR, DQ and DP types by a DNA—based system using sequence—specific oligonucleotides to probe amplified class II alleles amplified by the polymer—ase chain reaction. The expected associations with DR4 (relative risk 10,P<0.0001) and DR1 (relative risk 2.3, P<<0.001) were observed and only 13% of individuals lacked both of these alleles compared with 54% of age—and race—matched controls. A significant association with DRwlO (P = 0.02) was also observed in the DR4/DRl-negative RA group (3/23 patients compared with 0/54 DR4/DRl—negative controls). No novel associations with other DR, DQ, or DP alleles were evident in contrast to some previous studies. The third allelic hypervariable region of the DRp chain of DRwlO contains a similar amino acid sequence to that found in many DR4 and DR1 molecules. These results extend this correlation and suggest that this susceptibility determinant may account for the HLA-linked susceptibility in 89%of our cases of RA.

KEY WORDS: Disease susceptibility, Major histocompatibility complex, Sequence-specific oligonucleotides


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