KIR-like activating natural killer cell receptors and their association with complicated malaria in north India.

Killer immunoglobulin-like receptors (KIRs) genomic regions have been suggested to influence malaria pathogenesis and infection susceptibility. KIRs are known as activating natural killer (NK) cell receptors, which upon binding to their corresponding human leukocyte antigen (HLA) ligands cause lysis of any infected cell. We have examined the potential association of KIR genes with complicated malaria (CM) among north Indians in this study and further evaluated the KIR receptor-HLA ligand association on the severity of the disease considering the uncomplicated malaria (UCM) subjects as control. Molecular profiling of KIR and HLA was carried out using the PCR-SSP method. Susceptible association was found for individuals possessing KIR2DS2 (OR=1.76, p-value=0.0390), KIR2DL1 (OR=2.87, p-value=0.0005) and KIR2DL3 (OR=2.74, p-value=0.0011) genes with CM. This was supported by the strong linkage disequilibrium observed for 2DS2-2DL2 (D́=0.87, r=0.54) with CM. Whereas the receptor-ligand association has revealed risk association against KIR2DS2-HLAC1 (OR=2.08, p-value=0.0229), KIR2DL3-HLAC1 (OR=1.79, p-value=0.0301), and KIR2DL1-HLAC2 (OR=2.10, p-value=0.0175) combinations for complicated malaria. The frequency of different KIR genes are more or less similar to that observed in African population showing not much genetic diversity at KIR level in context to malarial infection. In conclusion, our data indicates KIR gene loci differentially influenced the malarial outcome in north Indians and in particular the KIR2DS2 gene appeared to be associated with disease severity.