Different KIRs confer susceptibility and protection to adults with latent autoimmune diabetes in Latvian and Asian Indian populations

KIRs (killer Ig-like receptors) expressed on natural killer (NK) cells are an important component of innate (and adaptive) immunity. They are either activatory or inhibitory, and certain KIRs are known to interact with specific motifs of HLA Class I molecules, which is very crucial in determining whether a cell is targeted to lysis or otherwise. Latent autoimmune diabetes in adults (LADA) is a slowly progressive form of autoimmune diabetes, with an adult onset (>30 years). Because autoantibodies and autoimmunity involved are involved in the etiology of LADA, KIRs might play an important role in conferring susceptibility to or protection against the disease. The purpose of this study was to identify killer immunoglobulin-like receptor (KIR) genes, which are associated with susceptibility to and protection against type 1 diabetes in Latvian and Asian Indian patients with LADA. KIR and HLA-C ligand genotyping was performed using PCR-SSP in LADA patients from Latvia (n = 45) with age- and sex-matched controls (n = 92) and from India (n = 86) with controls (n = 98). Results showed that in Latvian patients with LADA, KIRs 2DL1, 2DS2, and 2DS4 were associated with susceptibility and KIR 2DS5 with protection. In Asian Indian LADA patients, KIRs 2DL5 and 3DL1 were associated with susceptibility and KIRs 2DS1 and 2DS3 with protection. Stratification analyses for KIRs that bind to HLA-C1 and C2 were performed. We concluded that KIRs are important in conferring susceptibility (or protection) to adult patients with LADA in both our study populations. However the KIR genes (and their HLA-C ligands) conferring susceptibility or protection in these two populations differ, showing a role of ethnicity in disease susceptibility.