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We have investigated the role of HLA-DR genotypes in 184 patients with severe rheumatoid arthritis (RA) and in 46 patients with Felty syndrome, to establish the relative contribution of the RA-associated subtypes of DR4 (Dw4, Dw14, and Dw15). There was an excess of DR4 homozygotes, particularly Dw4/Dw14 compound heterozygotes (relative risk [RR] 49). The risk associated with Dw4 depended on the other allele present--Dw4/DR1 (RR 21), Dw4/Dw4 (RR 15), and Dw4/DRX (RR 6). There was a significant risk from Dw4/Dw14 compared with Dw4/Dw4, both in those with severe RA (RR 2.9; P less than .02) and in those with Felty syndrome (RR 4.2; P less than .02). In contrast, in a further 63 known DR4 homozygotes with RA, not selected for severe disease, the excess of Dw4/Dw14 was much less striking (RR 1.4; not significant), suggesting that this genotype may be particularly associated with more severe disease. We also found four cases with the rare Dw4/Dw15 genotype (expected less than or equal to 0.5; P less than or equal to .02). Since the Dw4, Dw14, Dw15, and DR1 molecules have similar antigen-binding sites and since combinations of these alleles particularly predispose to severe RA, we suggest that synergistic mechanisms are involved. These could include an effect on T-cell repertoire selection.
P Wordsworth, and
K D Pile, and
J D Buckely, and
J S Lanchbury, and
B Ollier, and
M Lathrop, and
J I Bell
August 1991,
European journal of immunogenetics : official journal of the British Society for Histocompatibility and Immunogenetics,
P Wordsworth, and
K D Pile, and
J D Buckely, and
J S Lanchbury, and
B Ollier, and
M Lathrop, and
J I Bell
November 1985,
Tissue antigens,
P Wordsworth, and
K D Pile, and
J D Buckely, and
J S Lanchbury, and
B Ollier, and
M Lathrop, and
J I Bell
January 1997,
Transplantation proceedings,
P Wordsworth, and
K D Pile, and
J D Buckely, and
J S Lanchbury, and
B Ollier, and
M Lathrop, and
J I Bell
April 1988,
Tissue antigens,
P Wordsworth, and
K D Pile, and
J D Buckely, and
J S Lanchbury, and
B Ollier, and
M Lathrop, and
J I Bell
April 1991,
British journal of rheumatology,
P Wordsworth, and
K D Pile, and
J D Buckely, and
J S Lanchbury, and
B Ollier, and
M Lathrop, and
J I Bell
January 2000,
Clinical and experimental rheumatology,
P Wordsworth, and
K D Pile, and
J D Buckely, and
J S Lanchbury, and
B Ollier, and
M Lathrop, and
J I Bell
June 1986,
Disease markers,
P Wordsworth, and
K D Pile, and
J D Buckely, and
J S Lanchbury, and
B Ollier, and
M Lathrop, and
J I Bell
January 2007,
BMC proceedings,
P Wordsworth, and
K D Pile, and
J D Buckely, and
J S Lanchbury, and
B Ollier, and
M Lathrop, and
J I Bell
June 1992,
Bailliere's clinical rheumatology,
P Wordsworth, and
K D Pile, and
J D Buckely, and
J S Lanchbury, and
B Ollier, and
M Lathrop, and
J I Bell
November 1990,
The Journal of rheumatology. Supplement,
