Association of Serum IL-17A Levels and IL-17/IL-17R Gene Variants with Community-Acquired Pneumonia in Iranian Children

Abstract

Background: Because the IL-17/IL-17 receptor (IL-17R) axis is involved in lung inflammation and genetic variants, such as single nucleotide polymorphisms (SNPs), can affect its function, this study examined the associations between IL-17/IL-17R gene SNPs, serum IL-17A levels, and community-acquired pneumonia (CAP) in Iranian children. Methods: A total of 266 subjects were enrolled in this study, comprising 126 children with CAP and 140 healthy controls. Genetic variants in the IL-17 and IL-17R genes were characterized by allele-specific PCR and PCR restriction fragment length polymorphism, respectively. Concurrently, serum IL-17A concentrations were measured by enzyme-linked immunosorbent assay. Results: Serum IL-17A levels were significantly higher in patients than in controls (295.8 ± 138.5 pg/mL vs. 40.6 ± 35.3 pg/mL, respectively; p = 0.001). Although the allele and genotype frequencies of IL-17 rs4711998 and IL-17 rs3748067 showed no significant association with CAP, the AA genotype and A allele of IL-17R rs4819554 were significantly more frequent in the patient group. Correlation analysis found no significant association between IL-17 genotypes and serum IL-17A levels. However, a significant positive correlation was observed between IL-17A levels and fever (p = 0.001). Conclusion: The upregulation of IL-17A in patient sera and its correlation with fever support a role for IL-17A in the pathogenesis of CAP. Furthermore, the A allele and AA genotype of IL-17R rs4819554 were identified as potential risk factors for CAP in Iranian children. The lack of a significant association between IL-17 gene variants and serum IL-17A levels may be attributable to the complex regulatory network governing IL-17 production.