2A-SS2-04

IMMUNOGENIC MARKER AND HLA GENOTYPE IN JAPANESE CHILDREN WITH TYPE 1 DIABETES MELLITUS

Sasaki N

Department of Pediatrics, Saitama Medical School

 

Objective: To elucidate the effect of HLA-associated genetic factors on the clinical heterogeneity of IDDM in Japanese people.

Methods. HLA-DRB1, DQA1, and DQB1 genotypes in 88 childhood-onset Japanese IDDM patients were examined.

Results: Of the 88 IDDM patients, 38 (43.2%) had DRB1*0901-DQA1*0302-DQB1*0303/X (DR9-DQ9/X), 26 (29.5%) had DRB1*0405-DQA1*0302-DQB1*0401/X (DR4-DQ4/X), and 9 (10.2%) were DR4/9-DQ4/9 heterozygous. The frequency of DR9-DQ9 genotype was significantly higher in the younger (0-10 years) than in the older (11-16 years) age-group of onset, but the frequency of DR4-DQ4 was higher in the older (11-16 years) age-group. Long-standing patients with DR9-DQ9 had significantly higher levels of GADAb than those with DR4-DQ4. The residual pancreatic β-cell function was retained more in patients with DR4-DQ4 than in those with DR9-DQ9 at diagnosis through 12-18 months after diagnosis.

Conclusion: These results suggest that the DR9-DQ9 genotype may induce stronger autoimmune destructive response against target β-cell than the DR4-DQ4 genotype does. Our findings may warrant further studies on the association of diabetogenic autoimmune response with HLA class II molecules and contribute to a clarification of interracial differences in HLA-encoded susceptibility to IDDM.