Closer association of IA-2 humoral autoreactivity with HLA DR3/4 than DQB1*0201/*0302 in Korean T1D patients

Abstract

The HLA DQB1*0302 allele on DR4 haplotypes is a well-known marker for T1D susceptibility. The contribution of this DQ molecule to overall disease susceptibility may be genotype dependent. On Asian DR4 haplotypes, not only DQB1*0302, but also DQB1*0401 confer susceptibility to T1D, which is mediated by DRB1*0405 on the same haplotype. To analyze further the association of DQB1*0302 and DQB1*0401 haplotypes in Asian patients with T1D, we investigated HLA DR and DQ alleles with the presence or the persistence of GAD, ICA, and IA-2 autoantibodies in 121 Korean T1D patients. In Korean patients, there was an association of IA-2 autoantibodies with DR4 as well as DR3, but not with DQA1*0301-DQB1*0302. GAD autoantibodies were not associated with the DR3-DQB1*0201, DQA1*0301-DQB1*0302, or DR4. In this low-risk population, autoantibodies to islet-cell antigens were associated with different HLA molecules. In different populations, the immune response to different beta cell autoantigens is mediated via varying HLA class II molecules from different loci. Design of the antigen-specific immunointervention trials should take into account such HLA DR and DQ association.