Interleukin-17A Serum Level, IL-17A Genetic Polymorphisms and Severe Malaria Disease

Abstract

Malaria infection is a multifactorial disease partly modulated by host immuno-genetic factors. Recent evidence has demonstrated the importance of Interleukin-17 family proinflammatory cytokines and their genetic variants in host immunity. However, limited knowledge exists about their role in parasitic infections such as malaria. We aimed to investigate IL-17A serum levels in patients with severe and uncomplicated malaria, whether IL-17A gene polymorphisms are involved in severe malaria susceptibility and the polymorphism’s influence on the IL-17A serum levels. 125 malaria patients and 48 free malaria controls were enrolled in this research. Malaria patients were classified into severe malaria (SM) and uncomplicated malaria (UM). IL-17A serum levels were measured with ELISA. PCR and DNA sequencing were used to assess host genetic polymorphisms in IL-17A. We performed a multivariate regression to estimate the impact of human IL-17A variants on IL-17A serum level and malaria outcome. Elevated serum IL-17A levels accompanied by increased parasitemia were found in SM patients compared to UM and controls (P<0.0001). Also, the IL-17A levels were lower in SM patients who were deceased than in those who survived. In addition, the minor allele frequencies (MAF) of two IL-17A polymorphisms (rs3819024 and rs3748067) were more prevalent in SM patients than UM patients indicating an essential role in SM. Interestingly, the heterozygous rs8193038 AG genotype was significantly associated with higher levels of IL-17A than the homozygous wild type (GG). According to our results, it can be concluded that IL-17A may play a role in protection against fatal malaria outcomes.