Skip to main content

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