Parity and placental infection affect antibody responses against Plasmodium falciparum during pregnancy

Abstract

Women are at higher risk of Plasmodium falciparum infection when pregnant. The decreasing risk of malaria with subsequent pregnancies is attributed to parity-dependent acquisition of antibodies against placental parasites expressing variant surface antigens, VAR2CSA, that mediate placental sequestration through adhesion to chondroitin sulfate A (CSA). However, modulation of immunity during pregnancy may also contribute to increase the risk of malaria. We compared antibody responses among 30 Mozambican primigravidae and 60 multigravidae at delivery, 40 men, and 40 children. IgG levels were measured against the surface antigens of erythrocytes infected with P. falciparum isolated from 12 pregnant women (4 placental and 8 peripheral blood isolates) and 26 nonpregnant hosts. We also measured IgG levels against merozoite recombinant antigens and total IgG. Placental P. falciparum infection was associated with increased levels of total IgG as well as IgG levels against merozoite antigens and parasite isolates from pregnant and nonpregnant hosts. We therefore stratified comparisons of antibody levels by placental infection. Compared to multigravidae, uninfected primigravidae had lower total IgG as well as lower levels of IgGs against peripheral blood isolates from both pregnant and nonpregnant hosts. These differences were not explained by use of bed nets, season at delivery, neighborhood of residence, or age. Compared to men, infected primigravidae had higher levels of IgGs against isolates from pregnant women and CSA-binding lines but not against other isolates, supporting the concept of a pregnancy-specific development of immunity to these parasite variants. Results of this study show that parity and placental infection can modulate immune responses during pregnancy against malaria parasites.

FIG. 1.

IgG levels (MFIs or ODs) in plasma samples from children and men residing in Manhiça, Mozambique, against merozoite antigens, P. falciparum laboratory lines, and field isolates. Vertical bars represent geometric mean levels of pooled MFIs or ODs, error bars the 95% confidence intervals, and P values the statistical significance of the results of univariate regression analysis with a robust variance estimator. Note that mean levels of IgG recognition by negative controls were as follows: of merozoite antigens, 0.24; CSA-binding lines, 7.60; non-CSA-binding lines, 6.83; placental isolates, 7.40; peripheral blood isolates from pregnant women, 3.89; and peripheral blood isolates from nonpregnant hosts, 2.15.

FIG. 2.

IgG levels (MFIs or ODs) in plasma samples from pregnant women with or without placental infection against merozoite recombinant antigens, P. falciparum laboratory lines, and field isolates. Vertical bars represent geometric mean levels of pooled MFIs or ODs, error bars the 95% confidence intervals, and P values the statistical significance of the results of regression analysis with a robust variance estimator (adjusted by age and parity).

FIG. 3.

IgG levels (MFIs or ODs) in plasma samples from pregnant women without (top) and with (bottom) placental P. falciparum infection by parity against merozoite recombinant antigens, P. falciparum laboratory lines, and isolates. Vertical bars represent geometric mean levels of pooled MFIs or ODs, error bars the 95% confidence intervals, and P values the statistical significance of the results of regression analysis with a robust variance estimator (adjusted by age).

FIG. 4.

IgG levels (MFIs or ODs) in plasma samples from men and primigravidae with placental infection (top) and from men and multigravidae with placental infection (bottom) against merozoite recombinant antigens, P. falciparum laboratory lines, and parasite isolates. Vertical bars represent geometric mean levels of pooled MFIs or ODs, error bars the 95% confidence intervals, and P values the statistical significance of the results of regression analysis with a robust variance estimator (adjusted by age).