ASSOCIATION OF SPECIFIC AMINO-ACID-SEQUENCE OF HLA-DR WITH RHEUMATOID-ARTHRITIS IN KOREANS AND ITS DIAGNOSTIC-VALUE

Objective, To analyze the association of susceptibility epitopes and a lleles of HLA-DRB1 with rheumatoid arthritis (RA) in Koreans. Methods, We performed HLA-DRB1 epitope typing in 61 patients and 82 controls u sing polymerase chain reaction (PCR) oligonucleotide hybridization, an d HLA-DR4, DR1, and DR8 alleles were characterized by PCR single stran d conformation polymorphism (SSCP). Results. The frequency of HLA-DR4 was significantly increased in patients with RA compared with controls (61 vs 29%; RR = 3.7, p < 0.0001). Epitope analysis revealed that sus ceptibility sequences in Korean patients with RA were (70)QRRA(74)A (5 2 vs 21%; RR = 4.2, p < 0.0001) and (70)QKRA(74)A (10 vs 1%; RR = 8.8, p < 0.05). The frequency of patients carrying either QRRAA or QKRAA a t the 70-74 position on the HLA-DR beta 1 molecule was significantly i ncreased compared with controls (57 vs 22%; RR = 4.8, p < 0.0001), Gen otypical analysis showed that DRB10405 and *0401 were the DR4 alleles associated with RA in Koreans (RR = 9.4, p < 0.00005; RR = 8.8, p < 0 .05, respectively), No significant differences were noted for other al leles including DRB10404 and DRB1*0101, QRRAA epitope typing was cons idered to have some diagnostic value for early RA. Conclusion. Our obs ervation indicates that a shared sequence (70)QR(K)RA(74)A, especially in HLA-DR4 subtypes, is strongly associated with RA in the Korean pop ulation. Additionally, the importance of DRB1()0405 in the pathogenes is of RA in East Asian ethnic groups was confirmed. These data suggest that not only the specific amino acid sequences but also the whole st ructure of the HLA-DR beta 1 molecule are important with regard to sus ceptibility to RA.