Importance of NFκβ, IL-10 serum levels and DC-SIGN polymorphic haplotypes in determining dengue disease severity among eastern Indian patients.

Abstract

Dengue viral (DENV) infection is most prevalent arboviral infection in India resulting in wide-range of symptomatic manifestation from simple (DF) to severe dengue (SD). DENV is internalized by dendritic cell receptor, DC-SIGN, which in turn activates inflammatory cytokines: NFκβ, IL-10 as adaptive immune response. Present study focused on role of DC-SIGN polymorphisms and these cytokines in SD development among eastern Indian patients. DC-SIGN polymorphisms (rs735239, rs4804803, rs2287886) and NFκβ, IL-10 concentrations were analysed among 179 dengue patients and 123 healthy individuals by PCR-RFLP and sandwich ELISA, respectively. DENV copies/ml and serotype in patient-sera were measured by quantitative and qualitative real time PCR, respectively. Statistical and haplotype analysis were performed by GraphPad-Prism and SNPStat, respectively. Prevalence of DENV serotypes among infected patients: DENV2>DENV4>DENV3>DENV1; those with DENV3 infection reported significantly increased IL-10 level. NFκβ and IL-10 concentrations were significantly elevated among SD patients. ROC curve analysis predicted cut-off values of NFκβ>13.46ng/ml and IL-10>490.5pg/ml to detect SD among infected patients with a good sensitivity and specificity. Patients with rs735239-GG, rs2287886-GG genotypes and GGG, GAG haplotypes were significantly associated with SD development, whereas, those with rs4804803-AG exhibited high DENVcopies/ml. Patients with these haplotypes also demonstrated increased NFκβ and IL-10. This study emphasised importance of DC-SIGN GGG and GAG haplotypes, NFκβ and IL-10 concentrations in WHO-defined severe dengue development among infected patients.