HLA genes associated with rheumatoid arthritis. Identification of susceptibility alleles using specific oligonucleotide probes.

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-DR beta 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.