Cell-mediated immune responses to Plasmodium falciparum purified soluble antigens in sickle-cell trait subjects

World Distribution, Population Genetics, and Health Burden of the Hemoglobinopathies

“…The protective effect of HbAS in naturally exposed populations increases with age (Cornille-Brogger et Guggenmoos-Holzmann et al 1981;Le Hesran et al 1999;Williams et al 2005a), indicating that the mechanism might not be entirely innate but might also include an acquired, immunological component. This hypothesis is supported by a number of studies that have reported enhanced malaria-specific immune responses in HbAS individuals (Edozien et al 1960;Marsh et al 1989;Bayoumi et al 1990;Abu-Zeid et al 1992;Odegbemi and Williams 1995;Cabrera et al 2005;Verra et al 2007a), and potentially by recent studies using a mouse model that suggest an immuno-modulatory mechanism mediated through hemoxygenase-1 (Ferreira et al 2011). However, the mouse model of the sickling disorders is metabolically very different to the human sickle-cell traits.…”

“…Recently, this relationship has been quantified statistically, an analysis that found strong geographical support for the malaria hypothesis in Africa but not in either the Americas or in Asia (Piel et al 2010). Hemoglobin S is absent from indigenous populations in the Americas, probably because malaria did not reach the continent until relatively recently, whereas in Asia it follows a rather Friedman 1978;Pasvol et al 1978;Friedman et al 1979 Enhanced removal of parasite-infected HbAS red blood cells Luzzatto et al 1970;Friedman 1978;Roth et al 1978;Shear et al 1993;Ayi et al 2004 Reduced pathogenicity of P. falciparum infected red blood cells because of reduced expression of PfEMP1 Cholera et al 2008;Cyrklaff et al 2011 Improved acquisition of malaria-specific immunity Edozien et al 1960;Cornille-Brogger et al 1979;Guggenmoos-Holzmann et al 1981;Marsh et al 1989;Bayoumi et al 1990;Abu-Zeid et al 1992 a thalassemia Specific protection against malaria-induced anaemia Allen et al 1997;Williams et al 2005d;Wambua et al 2006;May et al 2007;Fowkes et al 2008;Veenemans et al 2008 Reduced pathogenicity through reduced cytoadherence or rosetting Udomsangpetch et al 1993;Carlson et al 1994;Cockburn et al 2004 Immuological priming through crossspecies immunity between P. vivax and P. falciparum Williams et al 1996;Veenemans et al 2011 b thalassemia Enhanced removal of parasite-infected red blood cells Ayi et al 2004 Reduced invasion and growth of P. falciparum parasites Kaminsky et al 1986;Senok et al 1997 Reduced pathogenicity through reduced cytoadherence or rosetting restricted distribution, being confined to a small number of tribal populations in India …”

Impact of red blood cell polymorphisms on the antibody response to Plasmodium falciparum in Senegal

“…Hitherto, investigations of antibody responses with specificity for other P. falciparum asexual stage antigens have failed to detect differences in the prevalence or the magnitude of such responses in AS and AA children. It was notably the case for antibodies to infected erythrocytes, schizont extract, circumsporozoite protein, RESA and MSP1 in The Gambia [6,8], Sudan [38], and Gabon [39]. A single study reported lower prevalence rates of IgG to RESA in AS than in AA young Cameroonian children [10].…”

Biochemical and immunological mechanisms by which sickle cell trait protects against malaria

“…The mean lymphoproliferative response to affinity-purified P. falciparum soluble antigens [79-81] was found to be significantly higher in HbAS children compared to HbAA children [82-85] but a significant difference has not consistently been found between HbAA and HbAS adults [82,83]. Thus, available results suggest a more robust cellular response to P. falciparum in HbAS children.…”