Parity and Placental Infection Affect Antibody Responses againstPlasmodium falciparumduring 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 pregnancyspecific 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.

Immune responses during gestational malaria: a review of the current knowledge and future trend of research

“…The CSA adhesion phenotype is specific to placental parasites and it has been linked to the expression of a unique var gene (var2csa) [80,82]. The observation that men and children have equally poor IgG levels against parasite isolates compared to pregnant women and CSAbinding laboratory lines is consistent with the concept that immunity against VAR2CSA is acquired specifically during pregnancy [115]. Therefore, in Africa, immunity to CSA-binding parasites appears to be gender specific (thus men exposed to malaria lack these antibodies) [116,117] and parity related (thus antibodies increase during successive pregnancies) [111,116,117].…”

“…Exposition to infection throughout successive pregnancies has been associated with a lower risk of placental parasitemia [111], maternal anemia [118], low birth weight [115,118] and congenital malaria [119]. However, antibodies against P. falciparum antigens are not specifically associated with pregnancy, which have also been shown to increase with parity [115,120,121].…”

“…However, antibodies against P. falciparum antigens are not specifically associated with pregnancy, which have also been shown to increase with parity [115,120,121]. Moreover, a significant number of women at delivery have antibodies against placental parasites, but their placentas remain infected [111,116].…”

Pregnancy and Malaria Exposure Are Associated with Changes in the B Cell Pool and in Plasma Eotaxin Levels

“…Ab responses to placental P. falciparum isolates have been related to protection against malaria and to exposure to P. falciparum infections during pregnancy (11,12), and the levels of IgG correlate with parity in endemic areas (13,14). Although multiple studies have analyzed Ab responses to malaria parasites during pregnancy, only two recent studies have analyzed B cells in malaria during pregnancy.…”

Protection Against Malaria in Man: a Probe into some of the Implicated Mechanisms in Sub-Saharan Africa

“…This is due to the acquisition of parity-dependent antibodies against placental parasites expressing variant surface antigens, VAR2CSA, that modulates placental sequestration through linkage to chondroitin sulfate A (CSA) coupled with a low IgG response [58]. Since this immune response is mounted and increased with subsequent pregnancies, this may explain the higher predisposition of women in their first pregnancies.…”