Distribution of Killer cell immunoglobulin like receptor genes in end stage renal disease among North Indian population

Abstract

NK cell function is regulated by cell surface inhibitory and activating receptors including the C-type lectin receptors and Killer Immunoglobulin-like receptors (KIR). The effect of immune modulating cytokines produced by NK cells in the pathogenesis of end stage renal disease (ESRD) remained intriguing. In this regard the present study assesses the combinatorial association of KIR gene content and KIR receptor-HLA ligand in the North Indian ESRD patients. KIR gene polymorphism as a susceptible marker in ESRD among 512 patients and 512 ethnically matched controls was analyzed. PCR-SSP based genotyping for KIR gene content and HLA-A, B, C typing was carried out. Significant difference in frequencies of KIR2DS1-HLA-C2 (p≤0.0001, OR=1.98, CI=1.50-2.61), KIR2DS2-HLAC1 (p≤0.0001, OR=1.87, CI=1.42-2.46), KIR3DS1-HLA-Bw4 (p=0.0038, OR=1.46, CI=1.13-1.88) combinations for ESRD was found. In the combinatorial analysis Bw4(+)/3DL1(-)/3DS1(+) (p≤0.0001, OR=4.90, CI=2.75-8.71) and C1(+)/2DL2(-)/2DL3(-)/2DS2(+)/2DS3(+) (p=0.0037, OR=2.50, CI=1.35-4.63) showed risk association. KIR3DS1 was observed to be susceptible for all four primary kidney disease groups. NK cell de-regulation due to HLA ligand binding KIR receptors may be involved in the patho-physiology of ESRD. Upon analyzing the data in this context it was found that C2/C2 donor might improve the clinical outcome of patients having C2 ligands.