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Polymorphisms in the Fc Gamma Receptor IIIA and Toll-Like Receptor 9 Are Associated with Protection against Severe Malarial Anemia and Changes in Circulating Gamma Interferon Levels

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dc.contributor.author Munde, Elly O
dc.contributor.author Okeyo, Winnie A
dc.contributor.author Anyona, Samwel B
dc.contributor.author Raballah, Evans
dc.contributor.author Konah, Stephen
dc.contributor.author Okumu, Wilson
dc.contributor.author Ogonda, Lilian
dc.contributor.author Vulule, John
dc.contributor.author Ouma, Collins
dc.date.accessioned 2018-01-17T08:06:31Z
dc.date.available 2018-01-17T08:06:31Z
dc.date.issued 2012
dc.identifier.citation Munde, E. O., Okeyo, W. A., Anyona, S. B., Raballah, E., Konah, S., Okumu, W., … Ouma, C. (2012). Polymorphisms in the Fc Gamma Receptor IIIA and Toll-Like Receptor 9 Are Associated with Protection against Severe Malarial Anemia and Changes in Circulating Gamma Interferon Levels. Infection and Immunity, 80(12), 4435–4443. http://doi.org/10.1128/IAI.00945-12 en_US
dc.identifier.uri https://repository.maseno.ac.ke/handle/123456789/116
dc.description.abstract An understanding of the immunogenetic basis of naturally acquired immunity to Plasmodium falciparum infection would aid in the designing of a rationally based malaria vaccine. Variants within the Fc gamma receptors (FcγRs) mediate immunity through engagement of immunoglobulin G and other immune mediators, such as gamma interferon (IFN-γ), resulting in erythrophagocytosis and production of inflammatory cytokines in severe malarial anemia (SMA). The Toll-like receptors (TLRs) trigger transcription of proinflammatory cytokines and induce adaptive immune responses. Therefore, these receptors may condition malaria disease pathogenesis through alteration in adaptive and innate immune responses. To further delineate the impacts of FcγRIIIA and TLR9 in SMA pathogenesis, the associations between FcγRIIIA −176F/V and TLR9 −1237T/C variants, SMA (hemoglobin [Hb] < 6.0 g/dl), and circulating IFN-γ levels were investigated in children (n = 301) from western Kenya with acute malaria. Multivariate logistic regression analysis (controlling for potential confounders) revealed that children with the FcγRIIIA −176V/TLR9 −1237C (VC) variant combination had 64% reduced odds of developing SMA (odds ratio [OR], 0.36; 95% confidence interval [CI], 0.20 to 0.64; P = 0.001), while carriers of the FcγRIIIA −176V/TLR9 −1237T (VT) variant combination were twice as susceptible to SMA (OR, 2.04; 95% CI, 1.19 to 3.50; P = 0.009). Children with SMA had higher circulating IFN-γ levels than non-SMA children (P = 0.008). Hemoglobin levels were negatively correlated with IFN-γ levels (r = −0.207, P = 0.022). Consistently, the FcγRIIIA −176V/TLR9 −1237T (VT) carriers had higher levels of circulating IFN-γ (P = 0.011) relative to noncarriers, supporting the observation that higher IFN-γ levels are associated with SMA. These results demonstrate that FcγRIIIA-176F/V and TLR9 −1237T/C variants condition susceptibility to SMA and functional changes in circulating IFN-γ levels. en_US
dc.language.iso en en_US
dc.publisher American Society for Microbiology en_US
dc.title Polymorphisms in the Fc Gamma Receptor IIIA and Toll-Like Receptor 9 Are Associated with Protection against Severe Malarial Anemia and Changes in Circulating Gamma Interferon Levels en_US
dc.type Article en_US


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