ArticleInfection and immunity2012
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.
Article in Infection and immunity, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
7 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.
- Toll-like receptor 9 and 4 gene polymorphisms in susceptibility and severity of malaria: a meta-analysis of genetic association studies.Malaria journal · 2021Pooled it
- Polymorphisms in Fc Gamma Receptors and Susceptibility to Malaria in an Endemic Population.Frontiers in immunology · 2020Review
- Molecular basis of reduced LAIR1 expression in childhood severe malarial anaemia: Implications for leukocyte inhibitory signalling.EBioMedicine · 2019Article
- Modulation of Iron Metabolism in Response to Infection: Twists for All Tastes.Pharmaceuticals (Basel, Switzerland) · 2018Review
- Parasite Recognition and Signaling Mechanisms in Innate Immune Responses to Malaria.Frontiers in immunology · 2018Review
- Haplotype of non-synonymous mutations within IL-23R is associated with susceptibility to severe malaria anemia in a P. falciparum holoendemic transmission area of Kenya.BMC infectious diseases · 2017Article
- Association between Fcγ receptor IIA, IIIA and IIIB genetic polymorphisms and susceptibility to severe malaria anemia in children in western Kenya.BMC infectious diseases · 2017Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
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.
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Registered trials
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