Limited Neonatal Carbohydrate-Specific Antibody Repertoire Consecutive to Partial Prenatal Transfer of Maternal Antibodies.

Katharina Kappler,David F Smith,Yi Lasanajak,Thierry Hennet,Dirk Bassler,Tanja Restin

doi:10.3389/fimmu.2020.573629

Katharina Kappler, David F Smith + Show 4 more

Open Access

https://doi.org/10.3389/fimmu.2020.573629

Copy DOI

Abstract

Despite the prominence of carbohydrate-specific antibodies in human sera, data on their emergence and antigen specificities are limited. Whereas maternal IgG are transferred prenatally to the fetal circulation, IgM present in cord blood originate from fetal B lymphocytes. Considering the limited exposure of the fetus to foreign antigens, we assessed the repertoire of carbohydrate-specific antibodies in human cord blood and matched maternal blood samples using glycan arrays. Carbohydrate-specific IgM was absent in cord blood, whereas low cord blood IgG reactivity to glycans was detectable. Comparing IgG reactivities of matched pairs, we observed a general lack of correlation in the antigen specificity of IgG from cord blood and maternal blood due to a selective exclusion of most carbohydrate-specific IgG from maternofetal transfer. Given the importance of intestinal bacteria in inducing carbohydrate-specific antibodies, we analyzed global antibody specificities toward commensal bacteria. Similar IgG reactivities to specific Bacteroides species were detected in matched cord and maternal blood samples, thus pointing to an efficient maternal transfer of anti-microbial IgG. Due to the observed selectivity in maternofetal IgG transfer, the lack of fetal antibodies to carbohydrate epitopes is only partially compensated by maternal IgG, thus resulting in a weak response to carbohydrate antigens in neonates.

Highlights

Carbohydrate-specific antibodies represent a large fraction of circulating IgM and IgG
IgM concentration in cord blood increased with gestational age (Figure 1C), at term IgM concentration remained significantly lower than the concentration of about 1 mg/ml measured in maternal blood (Figure 1D, Supplementary Table 1)
To compare the antigenic repertoire of carbohydrate-specific antibodies in matched cord blood and maternal blood samples, we focused on neonates delivered at full term to maintain consistency in IgM and IgG levels

Summary

Introduction

Carbohydrate-specific antibodies represent a large fraction of circulating IgM and IgG. These antibodies mainly recognize alloantigens, such as ABO and Lewis blood groups [1, 2], and xenoantigens, including α-rhamnose, Forssman, and Galili antigens [3,4,5]. Antibodies to bacterial polysaccharides are mainly of IgG2 subclass, which is less efficiently transferred to the fetal circulation through FcRn [20]. The cord blood levels of IgG to xenoantigens, such as α-rhamnose and the Forssman antigen, and to bacterial lipopolysaccharides from Escherichia coli O16, O6, and O111 have been shown to be at least as high as in matched maternal samples [21, 22]

Methods

Results

Conclusion