ANALYSIS OF MHC CLASS-II ANTIGENS IN JAPANESE IDDM BY A NOVEL HLA-TYPING METHOD, HYBRIDIZATION PROTECTION ASSAY

We examined HLA Class II antigens in 116 Japanese IDDM patients [84 ty pical IDDM (T-IDD); 32 slowly progressive IDDM (S-IDD)] by the hybridi zation protection assay (HPA) which is a novel HLA typing method based on hybridization of acridinium-ester-labeled DNA probes to amplified DNA. We detected HLA-DRB1, -DQA1 and -DQB1 genes by this method which is capable of analyzing over 50 samples within 4 h with high sensitivi ty. Positive associations were found in DRB10405, DRB1*0802, DRB1*090 1, DQA10301, DQB1*0303 and DQB1*0401, negative correlations in DRB1*0 403, DR2, DR12, DRB10801 or 03, DQA1*0101 or 02, DQA1*0501, DQB1*0301 and DQB10602 alleles. The absence of aspartic acid (Asp) at position 57 of the DRB1 chain and the presence of arginine (Arg) at position 5 2 of the DQA1 chain correlated positively with both types of IDDM. The re were no significant differences in HLA between T-IDD and S-IDD. The se results suggest that the absence of Asp at position 57 of the DRB1 chain and the presence of Arg at position 52 of the DQA1 chain are sig nificant in Japanese IDDM patients and that DRB10802, in which the am ino acid at position 57 is aspartic acid, may play a role in the patho genesis of IDDM. Also, T-IDD and S-IDD have common bases in the HLA ge ne.