Significant differences in Fc[gamma]RIIa, Fc[gamma]RIIIa and Fc[gamma]RIIIb genes polymorphism and anti-malarial IgG subclass pattern are associated with severe Plasmodium falciparum malaria in Saudi children

• Published in: Malaria journal Vol. 20; no. 1
• Main Authors: Nasr, Amre, Aljada, Ahmad, Hamid, Osama, Elsheikh, Hatim A, Masuadi, Emad, Al-Bawab, Ahmad, Alenazi, Themer H, Abushouk, Amir, Salah, Ayman M
• Format: Journal Article
• Language: English
• Published: BioMed Central Ltd 22.09.2021
• Subjects: Antigen-antibody reactions; Drug therapy; Fc receptors; Genetic aspects; Genetic polymorphisms; Immunoglobulin G; Malaria; Pediatric research; Plasmodium falciparum; Risk factors; Saudi Arabia
• ISSN: 1475-2875; 1475-2875
• DOI: 10.1186/s12936-021-03901-0

Background The Fc[gamma]Rs 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 Fc[gamma]R (IIa, IIIa, and IIIb) genes polymorphism and the clinical outcome for anti-malarial antibody response of Plasmodium falciparum infection among Saudi children. Methods A total of 600 volunteers were 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 Fc[gamma]R genotypes were analysed using PCR amplification methods, and measurements of immunoglobulin were determined using enzyme-linked immunosorbent assay (ELISA) technique. Results The data revealed that the Fc[gamma]RIIa-R/R131 showed a statistically significant association with SM patients when compared to UM patients. Furthermore, higher levels of IgG1, IgG2, and IgG4 were associated with the Fc[gamma]RIIa-H/H131 genotype among UM patients. Although the Fc[gamma]RIIa-F/V176 genotype was not associated with UM, it showed a significant association with severe malaria. Interestingly, the Fc[gamma]RIIIa-V/V176 genotype offered protection against SM. Moreover, SM patients carrying the Fc[gamma]RIIIa-F/F genotype showed higher levels of AMA-1-specific IgG2 and IgG4 antibodies. The Fc[gamma]RIIIb-NA1/NA1 and Fc[gamma]RIIIb-NA2/NA2 genotypes did not show significant differences between the UM and the MFC groups. However, the genotype Fc[gamma]RIIIb-NA2/NA2 was statistically significantly associated with SM patients. Conclusions The data presented in this study suggest that the influence of the Fc[gamma]RIIa-R/R131, Fc[gamma]RIIIa-F/F176 and Fc[gamma]RIIIb-NA2/NA2 genotypes are statistically significantly associated with SM patients. However, the Fc[gamma]RIIa-H/H13 and Fc[gamma]RIIIa-V/V176 genotypes have demonstrated a protective effect against SM when compared to UM patients. The impact of the FcyR (IIa, IIIa and IIIb) gene variants and anti-malaria IgG subclasses play an important role in susceptibility to malaria infection and disease outcome in Saudi children. Keywords: Plasmodium, Falciparum, Malaria, IgG subclass, AMA-1, Saudi, Children