Significant Differences in FcγRIIa, FcγRIIa and FcγRIIIb Genes Polymorphism and Anti-malarial IgG Subclass Pattern are Associated with Severe Malaria in Saudi Children

Background: The FcyRs genotypes have been reported to play a key role in the defence against malaria parasites through both cellular and humoral immunity. This study aimed to investigate the possible correlation between FcγR (IIa, IIIa, and IIIb) genes polymorphism and the clinical outcome for anti‐malarial antibody response of Plasmodium falciparum infection among Saudi children. Material and methods: A 600 volunteers have been enrolled in this study, including 200 malaria-free control (MFC) subjects, 218 patients with uncomplicated malaria (UM) and 182 patients with severe malaria (SM). The FcγR genotypes was analysed using PCR amplification methods, and measurement of immunoglobulins were determine using ELISA. Results: The data revealed the FcγRIIa-R/R131 showed a statistically association with the increased susceptibility to SM when compared to UM patients. Furthermore, higher levels of IgG1, IgG2, and IgG4 were associated with the FcγRIIa-H/H131 genotypes among UM patients. Although the FcγRIIa-F/V176 genotype was not associated with UM, it showed a significant association with severe malaria. Interestingly, the FcγRIIa-V/V176 genotype was This study aimed to associated with protection against SM. Moreover, severe malaria patients carrying the FcγRIIa-F/F genotype showed higher levels of AMA-1-specific IgG2 and IgG4 antibodies. The FcγRIIIb NA1/NA1 and FcγRIIIb NA2/NA2 genotypes did not show significant differences between UM and the MFC. However, the genotype FcγRIIIb-NA2/NA2 was statistically associated with severe malaria. Conclusions: The data presented in this study strongly suggest the possible impact of FcyR (IIa, RIIIa and RIIIb) gene variants and anti-malaria IgG subclasses play a role in susceptibility to malaria infection and disease outcomes in Saudi children.