PfEMP1-Specific Immunoglobulin G Reactivity Among Beninese Pregnant Women With Sickle Cell Trait

Abstract

Background Sickle cell trait (HbAS) protects against severe Plasmodium falciparum malaria, but not against placental malaria (PM). In this study, PfEMP1-specific antibodies were measured in HbAA and HbAS Beninese pregnant women as a proxy of exposure to specific PfEMP1 variants. Methods Plasma samples collected at delivery from 338 HbAA and 63 HbAS women were used to measure IgG levels to six recombinant PfEMP1 proteins and three corresponding native proteins expressed on the infected erythrocyte (IE) surface. IgG-mediated inhibition of VAR2CSA + IEs adhesion to CSA was also tested. Results Levels of PfEMP1-specific IgG were similar in the two groups, except for native IT4VAR09 on IEs, where IgG levels were significantly higher in HbAS women. Adjusted odds ratios for women with positive IgG to HB3VAR06 and PFD1235w suggest a lower risk of infection with these virulent variants among HbAS individuals. The percentage of IEs binding to CSA did not differ between HbAA and HbAS women, but correlated positively with levels of anti-VAR2CSA and parity. Women with PM had lower levels of anti-VAR2CSA-specific IgG and lower IgG-mediated inhibition of IE adhesion to CSA. Conclusions The findings support similar malaria exposure in HbAA and HbAS women and a lack of HbAS-dependent protection against placental infection among pregnant women.

Impact of sickle cell trait hemoglobin inPlasmodium falciparum-infected erythrocytes

“…However, the possibility of parasites responding to this by qualitatively modulating PfEMP1 expression to avoid IE sequestration in tissues with low O 2 tension has not been investigated. There is some indirect support for this idea from studies showing that HbAS does not protect against placental malaria (47,48), characterized by selective IE sequestration in a high O 2 tension tissue (Fig. S1), and here we set out to provide additional evidence.…”

Impact of haemoglobinopathies on asymptomatic Plasmodium falciparum infection and naturally acquired immunity among children in Northern Ghana

“…However, no differences were found in Mali using a few PfEMP1 recombinant proteins (72). A recent study among HbAS and HbAC Beninese pregnant women showed no differences in the IgG levels to selected PfEMP1 variants (46,73). Hence analysis with a broader range of PfEMP1 variants would be more informative.…”

“…Levels of IgG specific for six recombinant P. falciparum proteins and crude 3D7 antigens were measured using an indirect ELISA, as reported (45,46). Briefly, 96-well flat-bottom microtiter plates (Nunc MaxiSorp; Thermo Fisher Scientific) were coated with 0.5 µg/mL of recombinant proteins (CSP, GLURP, PfMSP3, or Pfs230), 2µg/mL of the PfEMP1-type recombinant proteins or 5 × 10 5 IEs/ mL of the crude antigen lysate.…”

Plasmodium falciparum infection and naturally acquired immunity to malaria antigens among Ghanaian children in northern Ghana

“…Plasma IgG levels against four recombinant P. falciparum proteins and a crude parasite lysate were measured using indirect ELISA, as previously described ( Lopez-Perez et al, 2021 ). Briefly, 96-well flat-bottom microtitre plates (Nunc MaxiSorp; Thermo Fisher Scientific) were coated with 50 μL of recombinant protein (0.5 μg/mL) or crude antigen lysate (5 × 10 5 IEs/mL) in PBS and incubated overnight at 4 °C.…”