P080 : BIOLOGICAL SIGNIFICANCE OF HLA-G IN TYPE 1 DIABETES SUSCEPTIBILITY AMONG NORTH INDIANS

Abstract

Introduction T1D predisposition due to MHC region, particularly with HLA-DR3/DR4 and DQ2/DQ8 is reported worldwide, however not all DR3 or DR4 haplotypes predispose equally to the disease and role of several other genetic factors is also reported. HLA-G, a non classical HLA class I molecule with immunosuppressive role is involved in maintenance of tolerance and maintain the immune homeostasis in between aggressive and tolerable immune repertoire in various autoimmune diseases and transplantation. The HLA-G exon 8 14bp insertion/deletion polymorphism influences stability of mRNA and soluble HLA-G (sHLA-G) levels. Induction of HLA-G expression induced the inhibition of autologous T cell activation, indicating role in diabetes pathogenesis. Aim The present study was aimed at evaluating the possible association of 14bp INDEL polymorphism and soluble HLA-G with T1D in North Indian population. Study subjects included 85 T1D cases from our centre and ethnically matched 113 healthy controls (HCs). Results We analysed study cohort on the basis of HLA-G 14bp INDEL polymorphism and the presence/absence of the T1D susceptibility HLA allele (DR3). Among the DR3+ve group, the +/+ 14bp genotype was more common in patients than controls (32% vs 19%). On the other hand, −/−14bp was more frequent in the HCs (47% vs 31%) than patients. Similar analysis of DR3−ve cohort revealed that a higher number of T1D cases carried +/+ genotype (43% vs 22%). Further we observed higher soluble HLA-G in healthy cohort with +/+14bp polymorphism (51 ng/μl). Further, the soluble HLA-G analysis clearly indicated that the sHLA-G levels in T1D patients (with and without DR3 alleles) were lower in comparison to healthy controls (8 ng/μl vs 41 ng/μl). Again segregation of DR3 +ve and −ve T1D cohort on basis of the presence of 14bp INDEL polymorphism and soluble HLA-G levels, we observed decreased sHLA-G in DR3 positive T1D subjects with ins/ins 14bp in comparison to DR3negative with ins/ins14bp respectively (2 ng/μl vs 10 ng/μl). Conclusion These findings suggest combination of ins/ins 14bp genotype and the DR3 alleles probably induced the autoreactive T cells and sHLA-G may influence the balance of classical and non classical immune system in the diabetes pathogenesis in our study cohort.