Sean A Taylor1, Shilpee Sharma2, Christopher A L Remmel1, Beth Holder3, Christine E Jones4,5,6, Arnaud Marchant2, Margaret E Ackerman1. 1. Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire, USA. 2. Institute for Medical Immunology, Université Libre de Bruxelles, Brussels, Belgium. 3. Institute of Reproductive and Developmental Biology, Department of Metabolism, Digestion and Reproduction, Imperial College, London, United Kingdom. 4. Faculty of Medicine and Institute for Life Sciences, University of Southampton, Southampton, UK. 5. NIHR Southampton Clinical Research Facility, Southampton, UK. 6. NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
Abstract
BACKGROUND: Human immunodeficiency virus (HIV) infection during pregnancy is associated with reduced transplacental transfer of maternal antibodies and increased risk of severe infections in children who are exposed and uninfected with HIV. The basis of this reduced transfer of maternal immunity has not yet been defined but could involve modifications in the biophysical features of antibodies. The objective of this study was to assess the impact of maternal HIV infection on the biophysical features of serum IgG and transplacental antibody transfer. METHODS: Maternal serum IgG subclass levels, Fc glycosylation, Fc receptor (FcR) binding, and transplacental transfer of pathogen-specific maternal IgG were measured in pregnant women with HIV (WWH) and pregnant women testing negative for HIV (WNH) in Cape Town, South Africa. RESULTS: Maternal antibody profiles were strikingly different between pregnant WWH and WNH. Antibody binding to FcγR2a and FcγR2b, IgG1 and IgG3 antibodies, and agalactosylated antibodies were all elevated in WWH, whereas digalactosylated and sialylated antibodies were reduced compared to pregnant WNH. Antibody features that were elevated in WWH were also correlated with reduced transplacental transfer of vaccine antigen-specific antibodies. CONCLUSIONS: HIV infection is associated with marked alterations of biophysical features of maternal IgG and reduced placental transfer, potentially impairing antimicrobial immunity.
BACKGROUND: Human immunodeficiency virus (HIV) infection during pregnancy is associated with reduced transplacental transfer of maternal antibodies and increased risk of severe infections in children who are exposed and uninfected with HIV. The basis of this reduced transfer of maternal immunity has not yet been defined but could involve modifications in the biophysical features of antibodies. The objective of this study was to assess the impact of maternal HIV infection on the biophysical features of serum IgG and transplacental antibody transfer. METHODS: Maternal serum IgG subclass levels, Fc glycosylation, Fc receptor (FcR) binding, and transplacental transfer of pathogen-specific maternal IgG were measured in pregnant women with HIV (WWH) and pregnant women testing negative for HIV (WNH) in Cape Town, South Africa. RESULTS: Maternal antibody profiles were strikingly different between pregnant WWH and WNH. Antibody binding to FcγR2a and FcγR2b, IgG1 and IgG3 antibodies, and agalactosylated antibodies were all elevated in WWH, whereas digalactosylated and sialylated antibodies were reduced compared to pregnant WNH. Antibody features that were elevated in WWH were also correlated with reduced transplacental transfer of vaccine antigen-specific antibodies. CONCLUSIONS: HIV infection is associated with marked alterations of biophysical features of maternal IgG and reduced placental transfer, potentially impairing antimicrobial immunity.
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