Fc gamma Receptor IIa (CD32) Polymorphism and Antibody responses to Asexual Blood‐stage Antigens of Plasmodium falciparum Malaria in Sudanese Patients

Abstract

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.

FCGR2A functional genetic variant associated with susceptibility to severe malarial anaemia in Ghanaian children

“…Similarly, two studies on FcγRIIa polymorphisms in study cohorts from Kenya comprising 182 and 493 participants, respectively, provided evidence for protection against malaria by FcγRIIa 131RR , in these cases not against severe disease but against high parasite densities 17 18. On the other hand, one study from India with a total of 1871 individuals and a second study from Sudan investigating 256 individuals showed similar findings as ours but in differently defined malaria phenotypes and without discriminating between the various forms of disease 14 15. One possible explanation for these discrepancies may be different genetic backgrounds of the ethnically diverse study groups.…”

“…The effect of FcγRIIa H131R on malaria has been addressed in several studies but the data are difficult to interpret. The H allele was found associated with protection against severe malaria in Sudanese adults14 and FcγRIIa 131HH with protection against both severe and mild malaria in Indian adults 15. In contrast, the same variant was associated with susceptibility to severe malaria in Gambian children,16 and FcγRIIa 131RR was reported to protect against high parasite densities in Kenyan children 17 18…”

Genetic differentiation of populations residing in areas of high malaria endemicity in India

“…Apart from the fixation of α-thalassaemia in Indian Tharus, the high frequency of the FCGR2A exon 4 AA genotype that is significantly associated with protection from manifestation of falciparum malaria in India (Sinha et al 2008) may contribute to the resistance of Tharus to malaria. The association of the FCGR2A exon 4 AA genotype with protection from severe malaria has also been reported in New Halfa town population of eastern Sudan (Nasr et al 2007), as well as in our study on tribal populations of the Sundargarh district in Orissa (Sinha et al 2008). Of the remaining four SNPs that have been correlated with malaria severity/resistance in populations from Africa and Southeast Asia, none have been analysed for their association with falciparum malaria in India.…”

“…These SNPs have been previously correlated with malaria susceptibility/resistance primarily in African populations (McGuire et al 1994;Fernandez-Reyes et al 1997;Ubalee et al 2001;Mockenhaupt et al 2006;Nasr et al 2007). TNF-308 and TNF-238 SNPs are not in significant LD in Indian populations (r 2 = 0.022; determined from data on 55 Indian Genome Variation Consortium populations) and are thus unlikely to bias differentiation analysis (Sinha et al 2008).…”

The Levels of CD16/Fcγ Receptor IIIA on CD14+CD16+Monocytes Are Higher in Children with SeverePlasmodium falciparumAnemia than in Children with Cerebral or Uncomplicated Malaria

“…While one study found that the H/R genotype is more common in children at risk for severe malaria (50), other studies have shown an association between the H/H genotype or the H allele and severe malaria (10,38). Yet others have found no association (39) or that the H/H genotype is protective (33). The discrepancy in results likely comes from differences in study design, ethnic groups studied, and the pattern of malaria transmission at each study site.…”