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Abstract

We examined the association of individual HLA genes with rheumatoid arthritis (RA), using oligonucleotide probes that identified both DR4-associated and non–DR4-associated genes. Two distinct HLA–DRβ alleles (Dw4 and Dw14) were found in DR4+ RA patients compared with controls (Dw4 50% versus 17%; Dw14 35% versus 5%; total DR4 73% versus 30%), indicating that these 2 alleles are independent susceptibility genes. Remarkably, the majority of the DR4– RA patients also demonstrated a linear DNA sequence, apparently “shuffled” between different susceptibility alleles, identified with an oligonucleotide probe to a key portion of the Dw14 gene.