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Measuring Naturally Acquired Phagocytosis-Inducing Antibodies to Plasmodium falciparum Parasites by a Flow Cytometry-Based Assay
Published on: August 6, 2020
A macrophage migration inhibitory factor promoter polymorphism is associated with high-density parasitemia in
G A Awandare1, C Ouma, C C Keller
1Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Abstract:
Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that regulates innate and adaptive immune responses to bacterial and parasitic infections. Functional promoter variants in the MIF gene influence susceptibility to inflammatory diseases in Caucasians. As the role of genetic variation in the MIF gene in conditioning malaria disease outcomes is largely unexplored, the relationship between a G to C transition at MIF -173 and susceptibility to high-density parasitemia (HDP) and severe malarial anemia (SMA) was examined in Kenyan children (aged 3-36 months; n=477) in a holoendemic Plasmodium falciparum transmission region. In a multivariate model, controlling for age, gender, HIV-1 status, and sickle-cell trait, MIF -173CC was associated with an increased risk of HDP compared to MIF -173GG. No significant associations were found between MIF -173 genotypic variants and susceptibility to SMA. Additional studies demonstrated that homozygous G alleles were associated with lower basal circulating MIF levels relative to the GC group. However, stimulation of cultured peripheral blood mononuclear cells with malarial pigment (hemozoin) increased MIF production in the GG group and decreased MIF production in the GC group. Thus, variability at MIF -173 is associated with functional changes in MIF production and susceptibility to HDP in children with malaria.
Insights
Genetic variations in the macrophage migration inhibitory factor (MIF) gene influence malaria outcomes. The MIF -173CC genotype increases the risk of high-density parasitemia (HDP) in Kenyan children.
Area of Science:
- Immunogenetics
- Molecular Epidemiology
- Infectious Diseases
Background:
- Macrophage migration inhibitory factor (MIF) is a key cytokine regulating immune responses.
- Functional promoter variants in the MIF gene are linked to inflammatory diseases.
- The impact of MIF genetic variation on malaria susceptibility is understudied.
Purpose of the Study:
- To investigate the association between MIF -173 genetic variants and malaria disease outcomes in Kenyan children.
- To explore the relationship between MIF gene variability and susceptibility to high-density parasitemia (HDP) and severe malarial anemia (SMA).
Main Methods:
- A study involving 477 Kenyan children (aged 3-36 months) in a holoendemic malaria region.
- Genotyping for the MIF -173 G to C transition.
- Multivariate analysis controlling for age, gender, HIV-1 status, and sickle-cell trait.
Main Results:
- The MIF -173CC genotype was associated with an increased risk of HDP compared to the MIF -173GG genotype.
- No significant association was found between MIF -173 variants and SMA susceptibility.
- Homozygous G alleles correlated with lower basal MIF levels, while hemozoin stimulation altered MIF production differently between GG and GC genotypes.
Conclusions:
- MIF gene variability at the -173 position influences MIF production.
- MIF -173 genetic variants are associated with susceptibility to high-density parasitemia in children with malaria.
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