Structural and genetic features of human leukocytic antigen class II elements associated with rheumatoid arthritis.
Analysis of individual human leukocyte antigen (HLA) genes associated with rheumatoid arthritis was performed using oligonucleotide probes to identify putative susceptibility genes highly associated with disease. Among DR4-positive rheumatoid arthritis patients, two distinct DR-beta genes, Dw4 and Dw14, appear to be individual susceptibility alleles. Linked HLA genes at the DQ locus do not appear to contribute to this genetic risk. Among non-DR4 rheumatoid arthritis patients, a specific DNA sequence was identified that is shared by the Dw14 susceptibility gene and a majority of the non-DR4 rheumatoid arthritis patients. This sequence defines a specific small genetic element encoding a "Dw14 epitope" that appears to be a rheumatoid arthritis-associated risk factor indicative of a common genetic pathway in both DR4 and non-DR4-associated disease.
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Virginia Mason Research Center, Seattle, Washington, Immunology Research Program 98101.
D001172:Arthritis, Rheumatoid / Q000235:genetics*; D000939:Epitopes / Q000235:genetics; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006681:HLA-D Antigens / Q000235:genetics*; D006683:HLA-DQ Antigens / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics; D006801:Humans
D000939:Epitopes; D006681:HLA-D Antigens; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens