Table 1 Hypothesized protective mechanisms of sickle cell trait (HbAS) against malaria
From: Biochemical and immunological mechanisms by which sickle cell trait protects against malaria
Hypothesized mechanism of protection | Evidence | ||
|---|---|---|---|
Biochemical | HbAS changes how P. falciparum establishes an infection in the human host | P. falciparum induces sickling of red blood cells | Luzzatto 1970; Roth 1978 |
Reduced intra-erythrocytic growth of P. falciparum in HbAS red blood cells | Friedman 1978; Pasvol 1978; Roth 1978; La monte 2012 | ||
Reduced P. falciparum invasion of HbAS red blood cells | Luzatto 1970 | ||
P. falciparum induces changes in the red blood cell resulting in altered disease progression. | Reduced rosette formation | Carlson 1999 | |
Reduced cytoadherence | Cholera 2008 | ||
Immunological | Improved innate immune response | Enhanced phagocytosis of parasitized HbAS red blood cells | Ayi 2004; Urban 2006; Lang 2009 |
Improved acquired immune response | Epidemiologic evidence of an increase in protection against malaria with age in HbAS children | Guggenmoss-Holzmann 1981; Williams 2005; Gong 2012 | |
Increased cell mediated immune response | Increased lymphoproliferative response in HbAS children | Bayoumi 1990; Abu Zeid 1991; Abu Zeid 1992; Le Hesran 1999 | |
Increased humoral immune response | Higher IgG levels in HbAS individuals | Edozien 1960; Cornille-Brogger 1979; Verra 2008 | |
Higher levels of antibodies toward PfEMP-1 in HbAS individuals | Marsh 1989; Cabrera 2005; Verra 2008 | ||
Modulation of immunopathogenesis | Increased levels of HO-1 reduce inflammation irrespective of parasite load. | Ferreira 2011 | |