Abstract
Heterozygous hemoglobin (Hb) AS (sickle-cell trait) and HbAC are hypothesized to protect against Plasmodium falciparum malaria in part by enhancing naturally-acquired immunity to this disease. To investigate this hypothesis, we compared antibody levels to four merozoite antigens from the P. falciparum 3D7 clone (apical membrane antigen 1, AMA1-3D7; merozoite surface protein 1, MSP1-3D7; 175 kDa erythrocyte-binding antigen, EBA175-3D7; and merozoite surface protein 2, MSP2-3D7) in a cohort of 103 HbAA, 73 HbAS and 30 HbAC children aged 3 to 11 years in a malaria-endemic area of Mali. In the 2009 transmission season we found that HbAS, but not HbAC, significantly reduced the risk of malaria compared to HbAA. IgG levels to MSP1 and MSP2 at the start of this transmission season inversely correlated with malaria incidence after adjusting for age and Hb type. However, HbAS children had significantly lower IgG levels to EBA175 and MSP2 compared to HbAA children. On the other hand, HbAC children had similar IgG levels to all four antigens. The parasite growth-inhibitory activity of purified IgG samples did not differ significantly by Hb type. Changes in antigen-specific IgG levels during the 2009 transmission and 2010 dry seasons also did not differ by Hb type, and none of these IgG levels dropped significantly during the dry season. These data suggest that sickle-cell trait does not reduce the risk of malaria by enhancing the acquisition of IgG responses to merozoite antigens.
Highlights
Plasmodium falciparum malaria remains one of the greatest global health problems [1]
HbAS is associated with reduced malaria risk in Malian children In May 2009, we identified all HbAS (n = 73) and HbAC (n = 30) children in a cohort of Malian children from two villages
To explore whether IgG responses to merozoite antigens contributed to malaria protection in our sub-cohort of Malian children, we evaluated correlations between both ELISA and growth inhibition assay (GIA) data and malaria risk
Summary
Plasmodium falciparum malaria remains one of the greatest global health problems [1]. The mortality associated with this disease is believed to have evolutionarily selected for hemoglobin (Hb) S (b6 Glu to Val) in Africa This hypothesis is supported by epidemiological studies showing that heterozygosity for ‘adult’ HbA and ‘sickle’ HbS (HbAS, sickle-cell trait) protects children from developing severe, life-threatening malaria syndromes [2]. A recent study in mice has suggested that modulation of carbon monoxide levels by HbS may exert malaria-protective effects [9]. In addition to such innate factors, current studies have indicated that acquired immunity may contribute to the protective mechanism [3,10]. The effector mechanisms of this IgG-mediated protection and the impact of Hb variants on protective IgG responses have not been completely elucidated
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