Lack of an association between antibodies to Plasmodium falciparum glycosylphosphatidylinositols and malaria-associated placental changes in Cameroonian women with preterm and full-term deliveries

Abstract

Sequestration of Plasmodium falciparum parasites within the placenta often leads to an accumulation of macrophages within the intervillous space and increased production of tumor necrosis factor alpha (TNF-alpha), a cytokine associated with placental pathology and poor pregnancy outcomes. P. falciparum glycosylphosphatidylinositol (GPI) anchors have been shown to be the major parasite component that induces TNF-alpha production by monocytes and macrophages. Antibodies against P. falciparum GPI (anti-PfGPI), however, can inhibit the induction of TNF-alpha and inflammation. Thus, the study was undertaken to determine whether anti-PfGPI antibodies down-regulate inflammatory-type changes in the placentas of women with malaria. Anti-PfGPI immunoglobulin M (IgM) and IgG levels were measured in 380 pregnant women with or without placental malaria, including those who delivered prematurely and at term. Results showed that anti-PfGPI antibody levels increased with gravidity and age and that malaria infection boosted anti-PfGPI antibodies in pregnant women. However, no association was found between anti-PfGPI antibodies and placental TNF-alpha levels or the presence of acute or chronic placental malaria. Furthermore, anti-PfGPI antibody levels were similar in women with preterm and full-term deliveries and were not associated with an increase in infant birth weight. Thus, these results fail to support a strong role for anti-PfGPI antibodies in the prevention of chronic placental malaria infections and malaria-associated poor birth outcomes.

FIG. 1.

Anti-PfGPI antibody levels in malaria-negative, nonpregnant women and in pregnant women without and with placental malaria (Mal − and Mal +, respectively). Anti-PfGPI IgM (A) and IgG (B) levels were measured in the peripheral plasma, and results from antibody-positive women are displayed in box plots. The horizontal line within each box represents the median OD value, with the upper and lower vertical bars indicating the 90th and 10th percentiles, respectively. Anti-PfGPI IgM and IgG levels were significantly elevated in women with placental malaria compared to those without placental malaria. The Wilcoxon rank sum test was used for between-group comparisons.

FIG. 2.

Comparison of anti-PfGPI IgM and IgG levels between primigravidae (Primi) and multigravidae (Multi). Anti-PfGPI IgM (A) and IgG (B) levels in peripheral plasma of primigravidae and multigravidae, with or without placental malaria (Mal + and Mal −, respectively), are displayed in box plots. The horizontal line within each box represents the median OD value, with the upper and lower vertical bars indicating the 90th and 10th percentiles, respectively. Both anti-PfGPI IgM and IgG levels were significantly lower in malaria-negative primigravidae than in malaria-negative multigravidae. The Wilcoxon rank sum test was employed for between-group comparisons.

FIG. 3.

Scatter plots between TNF-α and anti-PfGPI antibodies. Anti-PfGPI IgM (A) and IgG (B) levels were plotted against their corresponding placental TNF-α concentrations within the same individual. Spearman's rho coefficient was measured to determine the degree of correlation between the variables.

FIG. 4.

Comparison of anti-PfGPI IgG and IgM levels in women with different stages of placental malaria infection. Anti-PfGPI IgM (A) and IgG (B) levels in the peripheral plasma of women with no evidence of placental infection or with acute, chronic, or past infections are displayed in box plots. The horizontal line within each box represents the median OD value, with the upper and lower vertical bars indicating the 90th and 10th percentiles, respectively. The Kruskal-Wallis test was employed for among-group comparisons.