Association between Fcγ receptor IIA, IIIA and IIIB genetic polymorphisms and susceptibility to severe malaria anemia in children in western Kenya

Munde, Elly O.; Okeyo, Winnie A.; Raballah, Evans; Anyona, Samuel B.; Were, Tom; Ong’echa, John Michael; Perkins, Douglas J; Ouma, Collins

doi:10.1186/s12879-017-2390-0

Cited by 23 publications

(37 citation statements)

References 54 publications

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“…These amino acid changes are responsible for antigenic determinants named human immunoglobulin Gm (gamma markers) allotypes. There are four allotypes for IgG1 in the CH1 and CH3 constant domains called G1m [1,2,3,17], one allotype for IgG2 in the CH2 constant domain called G2m23 and thirteen allotypes for IgG3 in the CH2 and CH3 constant domains called G3m [5,6,10,11,13,14,15,16,21,24,26,27,28] (12,13). The most polymorphic G3m allotypes are distinguished by variations on nine amino acids (13,14).…”

Section: Introductionmentioning

confidence: 99%

“…The presence of the FcgRIIA 131RH heterozygous polymorphism was associated with malaria protection in some studies (31,32) while for Maiga et al (33), a marginal protective effect on parasitemia was observed in a Fulani group from Mali harboring the 131RR genotype. Munde et al (11) demonstrated that the FcgRIIA 131R-FcgRIIIA 176F-FcgRIIIB NA2 haplotype was important in conditioning susceptibility to malaria anemia (or increased levels of circulating parasites) in West Kenya. Ouma et al (34) reinforced the results obtained from independent analysis of FcgR (31,32) by showing a negative association between the FcgRIIA 131H-FcgRIIIB NA1 haplotype and severe malaria anemia and a positive one when considering the FcgRIIA 131H-FcgRIIIB NA2 haplotype.…”

Section: Introductionmentioning

confidence: 99%

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Susceptibility to Plasmodium falciparum Malaria: Influence of Combined Polymorphisms of IgG3 Gm Allotypes and Fc Gamma Receptors IIA, IIIA, and IIIB

et al. 2020

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The binding of immunoglobulin (Ig) to Fc gamma receptors (FcgR) at the immune cell surface is an important step to initiate immunological defense against malaria. However, polymorphisms in receptors and/or constant regions of the IgG heavy chains may modulate this binding. Here, we investigated whether polymorphisms located in FcgR and constant regions of the heavy chain of IgG are associated with susceptibility to P. falciparum malaria. For this purpose, a clinical and parasitological follow-up on malaria was conducted among 656 infants in southern Benin. G3m allotypes (from total IgG3) were determined by a serological method of hemagglutination inhibition. FcgRIIA 131R/H and FcgRIIIA 176F/V genotypes were determined using the TaqMan method and FcgRIIIB NA1/NA2 genotypes were assessed by polymerase chain reaction using allele-specific primers. Association analyses between the number of malaria infections during the follow-up and polymorphisms in IgG G3m allotypes and FcgR were studied independently by zero inflated binomial negative regression. The influence of combinations of G3m allotypes and FcgRIIA/FcgRIIIA/FcgRIIIB polymorphisms on the number of P. falciparum infections, and their potential interaction with environmental exposure to malaria was assessed by using the generalized multifactor dimensionality reduction (GMDR) method. Results showed that individual carriage of G3m24 single allotype and of G3m5,6,10,11,13,14,24 phenotype was independently associated with a high risk of malaria infection. A risk effect for G3m6 was observed only under high environmental exposure. FcgRIIIA 176VV single genotype and combined carriage of FcgRIIA 131RH/FcgRIIIA 176VV/FcgRIIIB NA1NA2, FcgRIIA 131HH/FcgRIIIA 176FF/FcgRIIIB NA1NA1, FcgRIIA 131HH/FcgRIIIA 176VV/FcgRIIIB NA2NA2 and FcgRIIA 131HH/FcgRIIIA 176VV/FcgRIIIB NA1NA2 genotypes were related to a high number of malaria infections. The risk was accentuated for FcgRIIIA 176VV when considering the influence of environmental exposure to malaria. Finally, the GMDR analysis including environmental exposure showed strengthened associations with a malaria risk when FcgRIIA/FcgRIIIA/FcgRIIIB genotypes were combined to G3m5,6,11,24 and G3m5,6,10,11,13,15,24 phenotypes or G3m10 and G3m13 single allotypes. Our results highlight the relevance of studying IgG heavy chain and FcgR polymorphisms, independently as well as in combination, in relation to the individual susceptibility to P. falciparum infection. The intensity of individual exposure to mosquito bites was demonstrated to impact the relationships found.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Susceptibility to Plasmodium falciparum Malaria: Influence of Combined Polymorphisms of IgG3 Gm Allotypes and Fc Gamma Receptors IIA, IIIA, and IIIB

et al. 2020

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“…SMA typically occurs in areas that have high exposure rates to Plasmodium or are genetically susceptible to the disease. FcγRIIIa is the lone Fc receptor expressed on NK cells that enables ADCC, and polymorphisms in FcγRIIIa are associated with SMA [97]. The cell responsible for this association is unknown, but lack of function mutations correlate with poorer outcomes.…”

Section: Introductionmentioning

confidence: 99%

Contributions of natural killer cells to the immune response against Plasmodium

Burrack

Hart

Hamilton

2019

Malar J

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Natural killer (NK) cells are important innate effector cells that are well described in their ability to kill virally-infected cells and tumors. However, there is increasing appreciation for the role of NK cells in the control of other pathogens, including intracellular parasites such as Plasmodium, the cause of malaria. NK cells may be beneficial during the early phase of Plasmodium infection—prior to the activation and expansion of antigen-specific T cells—through cooperation with myeloid cells to produce inflammatory cytokines like IFNγ. Recent work has defined how Plasmodium can activate NK cells to respond with natural cytotoxicity, and inhibit the growth of parasites via antibody-dependent cellular cytotoxicity mechanisms (ADCC). A specialized subset of adaptive NK cells that are negative for the Fc receptor γ chain have enhanced ADCC function and correlate with protection from malaria. Additionally, production of the regulatory cytokine IL-10 by NK cells prevents overt pathology and death during experimental cerebral malaria. Now that conditional NK cell mouse models have been developed, previous studies need to be reevaluated in the context of what is now known about other immune populations with similarity to NK cells (i.e., NKT cells and type I innate lymphoid cells). This brief review summarizes recent findings which support the potentially beneficial roles of NK cells during Plasmodium infection in mice and humans. Also highlighted are how the actions of NK cells can be explored using new experimental strategies, and the potential to harness NK cell function in vaccination regimens.

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“…Indeed, the frequencies of the H131 and R131 alleles vary according to ethnic grouping in Africa. Three different studies showed similar distributions of H131 homozygotes (27.37% out of 274 subjects, 32% out of 97 subjects, and 20.45% out of 88 subjects) in Luo and Luhya populations of Kenya and a Yoruba population of Nigeria (56,60). However, different distributions of the genotype for this SNP were found for different ethnic groups from Ghana (p=0.036), with the frequency of subjects who were homozygous for R131 being higher for the Ga-Adangbe ethnic group than for the Akan, Hausa and Fulani ethnic groups (p=0.01347; Chi square test performed by us and R according to the results given by the authors in the Supplementary Table in SI) (93).…”

Section: Genes Encoding Low-affinity Receptorsmentioning

confidence: 78%

Polymorphisms in Fc Gamma Receptors and Susceptibility to Malaria in an Endemic Population

et al. 2020

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Repeated infections by Plasmodium falciparum result in a humoral response that could reduce disease symptoms and prevent the development of clinical malaria. The principal mechanism underlying this humoral response is that immunoglobulin G (IgG) binds directly to the parasites, thus causing their neutralization. However, the action of antibodies alone is not always sufficient to eliminate pathogens from an organism. One key element involved in the recognition of IgG that plays a crucial role in the destruction of the parasites responsible for spreading malaria is the family of Fc gamma receptors. These receptors are expressed on the surface of immune cells. Several polymorphisms have been detected in the genes encoding these receptors, associated with susceptibility or resistance to malaria in different populations. In this review, we describe identified polymorphisms within the family of Fc gamma receptors and the impact of these variations on the response of a host to infection as well as provide new perspectives for the design of an effective vaccine for malaria.

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Association between Fcγ receptor IIA, IIIA and IIIB genetic polymorphisms and susceptibility to severe malaria anemia in children in western Kenya

Cited by 23 publications

References 54 publications

Susceptibility to Plasmodium falciparum Malaria: Influence of Combined Polymorphisms of IgG3 Gm Allotypes and Fc Gamma Receptors IIA, IIIA, and IIIB

Susceptibility to Plasmodium falciparum Malaria: Influence of Combined Polymorphisms of IgG3 Gm Allotypes and Fc Gamma Receptors IIA, IIIA, and IIIB

Contributions of natural killer cells to the immune response against Plasmodium

Polymorphisms in Fc Gamma Receptors and Susceptibility to Malaria in an Endemic Population

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