Parasitic infections during pregnancy in Gabon affect glycosylation patterns of maternal and child antibodies

Abstract

Antibody glycosylation patterns can affect antibody functionality and thereby contribute to protection against invading pathogens. During pregnancy, maternal antibodies can be transferred through the placenta and contribute to modulating both the mother's and her child's immune responses. Although several studies of IgG glycosylation during pregnancy have been carried out, very few cohorts studied were from sub-Saharan Africa, where exposure to microorganisms and parasites is high. In Lambaréné, Gabon, 106 pregnant women in their third trimester were enrolled into this study. At enrolment, urine, stool, and blood samples were collected from the mothers to assess Schistosoma haematobium (S. haematobium), Plasmodium falciparum (P. falciparum) and other parasite infections. During delivery, cord blood samples were collected. The children were followed, and blood samples were collected at 9 and 12 months of age. IgG Fc glycosylation was measured by liquid chromatography-mass spectrometry, determining fucosylation, galactosylation, sialylation, bisection, and sialylation per galactose (SA/gal). Among the 106 pregnant women, 33 (31%) were infected by at least one parasite. The antibody glycosylation patterns in maternal and cord blood showed distinct profiles when compared to that of infants at 9 and 12 months. IgG galactosylation was higher in maternal/cord blood, while fucosylated IgG was higher in children up to 1 year of age. Maternal parasitic infection was associated with lower IgG2 and IgG3/IgG4 galactosylation in cord blood and lower IgG3/IgG4 galactosylation in children. When maternal IgG galactosylation and, consequently, cord blood were categorized as high, children at 9 and 12 months of age showed higher IgG galactosylation compared to children of mothers with low IgG galactosylation. As IgG Fc galactosylation can have functional consequences, it might provide valuable information for developing effective preventive and treatment strategies for vulnerable populations.

Keywords: Antibody; Child; Gabon; Glycosylation; Parasitic infections; Pregnancy.

Fig. 1

Characteristics of the maternal infection status. The parasite counts among mothers are shown in this figure. The bar graph on the left shows the total count of each parasite detected among mothers, including Strongyloides stercoralis (S. stercoralis), Ascaris lumbricoides (A. lumbricoides), Plasmodium falciparum (P. falciparum), Hookworm, Loa loa (L. loa), Schistosoma haematobium (S. haematobium), and Trichuris trichiura (T. trichiura). The intersection matrix on the right indicates the co-infection of different parasites in individual mothers, with bars representing the number of mothers infected with each (poly)parasite. Each dot in the matrix corresponds to the presence of a specific parasite in the intersection group.

Fig. 2

Principal Component Analysis of IgG antibody glycosylation in maternal, cord, and child at 9- and 12-months blood. Principal component analysis (PCA) of IgG antibody glycosylation patterns. (A) PCA plot showing the distribution of samples based on common glycan structures. Each point represents a single sample, colour-coded by population (mother, cord blood, child at 9 months, child at 12 months) and shaped by maternal infection status (negative or positive). (B) Variables PCA plot showing the contribution of different glycosylation features to the principal components. PC1 explains 45% of the variance, while PC2 explains 25.3%.

Fig. 3

IgG galactosylation and IgG fucosylation in different samples: maternal, cord, and child 9 and 12 months blood. Violin plots show the glycosylation trait distribution in IgG subclasses among different populations (mother, cord blood, child at 9 and 12 months). Each plot represents the percentage of total glycan structures for a specific trait: (A) IgG1 galactosylation, (B) IgG1 fucosylation, (C) IgG2 galactosylation, (D) IgG2 fucosylation, (E) IgG3/IgG4 galactosylation. Asterisks indicate statistical significance between groups (ns: not significant, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001).

Fig. 4

Comparison of the IgG galactosylation in different samples (maternal, cord, and child at 9 and 12 months blood) based on maternal infection status. Violin plots showing the percentage for each trait of total glycan structures in IgG subclasses between different populations based on maternal infection status (negative vs. positive). The plots are divided by sample type (mother, cord blood, child at 9 and 12 months): (A) IgG1 galactosylation, (B) IgG2 galactosylation, (C) IgG3/IgG4 galactosylation. Asterisks indicate statistical significance between groups (ns: not significant, *p < 0.05, **p < 0.01, ***p < 0.001).

Fig. 5

Comparison of sub-classes of IgG galactosylation levels in different samples (maternal, cord, child at 9 and 12 months blood). Longitudinal analysis of IgG galactosylation patterns across different time points and groups. (A: IgG1 galactosylation, B: IgG2 galactosylation and C: IgG3/IgG4 galactosylation). Line plots showing the percentage of total glycan structures for IgG1, IgG2, and IgG3/IgG4 galactosylation from mother to child (9 and 12 months), categorized into three steady groups: high, medium, and low. (D) Plots showing the progression of IgG1 galactosylation levels (low, medium, high) from mother to cord blood and from cord blood to child at 9 and 12 months. These plots illustrate the changes in galactosylation levels over time for each group. The steady groups help to visualize the stability or changes in glycosylation patterns across the different stages of development.