In a prospective clinical study in New Halfa Teaching Hospital, the possible association between FcγRIIa‐R/H131 polymorphism and anti‐malarial antibody responses with clinical outcome of Plasmodium falciparum malaria among Sudanese patients was investigated. A total of 256 individuals were consecutively enrolled, comprising 115 patients with severe malaria, 85 with mild malaria and 56 malaria‐free controls. Genotyping of FcγRIIa‐R/H131 dimorphism was performed using gene‐specific polymerase chain reaction (PCR) amplification with allele‐specific restriction enzyme digestion of the PCR product. The antibody responses to asexual blood‐stage antigens were assessed by an enzyme‐linked immunosorbent assay. The frequency of the FcγRIIa‐R/R131 genotype was significantly higher in those with severe malaria when compared with patients with mild malaria, while the FcγRIIa‐H/H131 genotype showed a significant association with mild malaria. A reduced risk of severe malaria with IgG3 antibodies in combination with the H/H131 genotype was observed. Furthermore, low levels of IgG2 antibodies reactive with the Pf332‐C231 antigen were also associated with lower risk of severe malaria in individuals carrying the H131 allele. The levels of IgG1 and IgG3 antibodies were statistically significantly higher in the mild malaria patients when compared with the severe malaria patients. Taken together, our study revealed that the FcγRIIa‐R/R131 genotype is associated with the development of severe malaria, while the H/H131 genotype is more likely to be associated with mild malaria. Our results also revealed that the natural acquisition of immunity against clinical malaria appeared to be more associated with IgG1 and IgG3 antibodies, signifying their roles in parasite‐neutralizing immune mechanisms.

Background: A SNP at position 131, in the FcγRIIa gene, affects the binding of the different IgG subclasses and may influence the clinical variation seen in patients with falciparum malaria. This study confirms and extends previous findings, analysing the FcγRIIa (CD32) polymorphism in relation to the IgG subclass distribution seen among two sympatric tribes living in eastern Sudan, characterized by marked differences in susceptibility to Plasmodium falciparum malaria.

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