The effect of KIR and HLA polymorphisms on dengue infection and disease severity in northeastern Thais

Killer cell immunoglobulin-like receptors (KIRs) are cell surface receptors on natural killer (NK) cells and subsets of T cells. The interaction between KIRs and their cognate ligands (Human leukocyte antigen class I molecules, HLA class I) modulates the immune response of NK cells, in particular through clearance of virus-infected cells. Here, we investigated the effect of KIRs and HLA ligands on dengue infections and disease severity. The KIRs and HLA ligands were identified in 235 healthy controls (HC) and 253 dengue patients (DEN) using polymerase chain reaction with sequence specific primer (PCR-SSP); moreover, DEN was classified to 100 dengue fever (DF) and 153 dengue haemorrhagic fever (DHF). Risks were expressed as odds ratios (ORs) and 95% confidence intervals (CIs) with significance set at a two-tailed P value of < 0.05. The Bonferroni correction was applied for multiple comparisons. Twelve significant associations were observed in dengue infections and disease severity; however, two outcomes survived after the Bonferroni correction. Of these, HLA-A11 was associated with an increased risk to develop dengue disease (OR 2.41, 95% CI 1.62-3.60, P^c = 0.004), while KIR3DS1⁺ Bw4 was a protective genotype to developing DHF (OR 0.28, 95% CI 0.16-0.48, P^c < 0.001). This study revealed an important role of KIR and HLA ligands in innate immune responses to dengue viral infections and, in particular, their effect on clinical outcomes and disease severity.