To reveal immunogenetic factors involved in the pathogenesis of
rheumatoid arthritis(RA), two hundreds and four unrelated Japanese patients with RA were typed for HLA by both serologic typing and DNA typing using polymerase chain reaction-sequence specific
oligonucleotide probe (PCR-SSOP) method. Serologic HLA typing data showed that frequencies of
HLA-A11, DR4, DR53, and DQ4 were increased and those of DR8, DR52, and DQ1 were decreased in the patient group. The HLA-DNA typing has defined more precisely the disease-associated HLA-class II alleles and revealed that DRB1*0405, DQA1*03, and DQB1*0401 were strongly associated with the
disease susceptibility whereas DRB1*0803, DQA1*0103, and DQB1*0601 showed negative association with RA. Comparison of amino acid sequences of DRB1*0405 with other DRB1 alleles suggested that the risk for RA was closely associated with particular
amino acid residues of DR beta chain, i. e.
glycine residue at the 86th position in addition to the residues between 70th and 74th position. The significant decreased frequency of DRB1*0803 in the DRB1*0405 positive patient group suggests that DRB1*0803 may control resistance to RA as a dominant genetic trait. In addition, the observation that the frequency of DPB1*0201 was increased in the DRB1*0405 negative patient group may indicate that the
disease susceptibility to RA is controlled by the
HLA-DP region in the minority of the patients. The polymorphism of TAP2 gene and TCR genes showed no significant association with RA, suggesting that the contribution of these genes to the susceptibility is relatively small, if any.