Natural Acquired Immunity to Malaria Antigens among Pregnant Women with Hemoglobin C Trait

Abstract

Hemoglobin C is the second most common structural hemoglobinopathy in Africa, and carriers have a reduced risk of severe malaria. However, the effect of HbAC on the antibody response to malaria antigens in pregnancy has not been studied. Here, we measured PfEMP1-specific antibodies in plasma samples from 74 Beninese pregnant women with either HbAA or HbAC. IgG-mediated inhibition of VAR2CSA+ infected erythrocytes adhesion to chondroitin sulfate A (CSA) was also tested. PfEMP1-specific IgG levels to VAR2CSA were significantly lower in HbAC women, suggesting less exposure to VAR2CSA. In contrast, the percentage of VAR2CSA+-infected erythrocytes adhesion to CSA was not different between HbAA and HbAC women. Moreover, IgG levels to PfEMP1 variants associated with severe malaria were not significantly different between groups. The findings indicate similar exposure to Plasmodium falciparum parasites expressing PfEMP1 variants causing severe malaria, and justify more comprehensive studies of hemoglobinopathy-related qualitative and quantitative differences in PfEMP1-specific antibody responses.

Figure 1.

Antibody response to VAR2CSA and inhibition of binding to chondroitin sulfate A (CSA). Recombinant and native VAR2CSA-specific IgG levels determined by an ELISA (n = 74) and flow cytometry (n = 67) are expressed in arbitrary units and normalized mean fluorescence intensity (nMFI), respectively. Inhibition of infected erythrocytes adhesion to CSA at delivery is expressed as a percentage (n = 70). IgG levels against R0 domain of glutamate-rich protein (GLURP) as determined by an ELISA (n = 74) are expressed in arbitrary units. Median, interquartile range (IQR), and whiskers (1.5 times the IQR) are shown. Dotted line indicates the threshold of positivity. P values using Mann-Whitney U test are also indicated. This figure appears in color at www.ajtmh.org.

Figure 2.

Antibody response to recombinant non-VAR2CSA PfEMP1 proteins. IgG levels against full-length recombinant proteins HB3VAR06, IT4VAR09, and IT4VAR60, or single DBLβ domains of HB3VAR34 and PFD1235w were determined by ELISA (n = 74). In all panels, the values are expressed in arbitrary units. Median, interquartile range (IQR), whiskers (1.5 times the IQR), and outliers are shown. Dotted line indicates the threshold of positivity. P values using Mann-Whitney U test are also indicated. This figure appears in color at www.ajtmh.org.