title: Sickle cell trait is associated with controlled levels of haem and mild proinflammatory response during acute malaria infection.
abstract: The controlled induction of haemoxygenase-1 (HO-1), an enzyme that catabolizes haem, has been shown to reduce haem, preventing pathologies associated with haem toxicity. The hemoglobin genotype HbAS confers reduced susceptibility to severe complications of malaria by a mechanism that is not well understood. Using a longitudinal approach, we investigated the effect of baseline concentrations of HO-1 on the accumulation of haem during acute Plasmodium falciparum malaria in HbAS and HbAA genotypes. Plasma concentrations of haem, HO-1 and cytokines were quantified in venous blood obtained from children (9 months-5 years of age) during malaria infection, and at convalescence (baseline levels). Parasitaemia was determined during malaria infection. In patients with the HbAA genotype, there was a significant elevation in the plasma concentration of haem (P = 0.002), and a consequent increased induction of HO-1 (P < 0.001) during falciparum malaria compared with levels at convalescence. Contrary to HbAA, plasma concentration of haem did not change in the HbAS genotypical group (P = 0·110), and the induction of HO-1 was reduced during malaria compared with levels at convalescence (P = 0·006). Higher plasma levels of haem were observed in HbAS compared with HbAA at convalescence (P = 0·010), but this difference did not affect the levels of HO-1 within each genotype (P = 0·450). Relatively milder proinflammatory responses were observed in HbAS children during malaria infection compared to HbAA children. Our findings suggest that a mechanism of reduced susceptibility to severe malaria pathologies by the HbAS genotype may involve the control of haem, leading to controlled levels of HO-1 and milder proinflammatory responses during acute malaria.
authors.affiliation: West African Centre for Cell Biology of Infectious Pathogens, Department of Biochemistry, Cell and Molecular Biology, College of Basic and Applied Sciences, University of Ghana, Legon, Ghana.|Institute of Child Health, University of Ibadan, Nigeria.
authors.forename: T W
authors.initials: TW
authors.lastname: Ademolue
authors.affiliation: Institute of Child Health, University of Ibadan, Nigeria.
authors.forename: O K
authors.initials: OK
authors.lastname: Amodu
authors.affiliation: West African Centre for Cell Biology of Infectious Pathogens, Department of Biochemistry, Cell and Molecular Biology, College of Basic and Applied Sciences, University of Ghana, Legon, Ghana.
authors.forename: G A
authors.identifier: 0000-0002-8793-3641
authors.initials: GA
authors.lastname: Awandare
mesh_terms: D002675:Child, Preschool; D003289:Convalescence; D016207:Cytokines / Q000097:blood; D005260:Female; D005838:Genotype; D006418:Heme / Q000032:analysis*; D051547:Heme Oxygenase-1 / Q000097:blood*; D006454:Hemoglobins / Q000235:genetics; D006801:Humans; D007223:Infant; D007249:Inflammation; D008288:Malaria / Q000097:blood / Q000276:immunology / Q000469:parasitology; D016778:Malaria, Falciparum / Q000097:blood* / Q000150:complications* / Q000276:immunology / Q000469:parasitology; D008297:Male; D010963:Plasmodium falciparum / Q000276:immunology / Q000302:isolation & purification; D012805:Sickle Cell Trait / Q000150:complications* / Q000276:immunology
chemical_list: D016207:Cytokines; D006454:Hemoglobins; D006418:Heme; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1
keywords: haem; haemoxygenase-1; malaria; sickle cell trait