Abstract
Maternal asthma during pregnancy is considered an environmental risk factor for asthma development in children. Immunoglobulin G (IgG) antibodies that are transferred from the mother to the fetus are known to act in a pro- or anti-inflammatory manner depending on their glycosylation status. Using a mouse model, we examined how maternal allergic airway inflammation during pregnancy influenced offspring experimental asthma severity, as well as maternal and offspring serum IgG antibody glycosylation patterns. Additionally, the effects of maternal and offspring exposure to the same or different allergens were investigated. Female mice were either sham sensitized or sensitized to casein (CAS) or ovalbumin (OVA) before mating. Subsequently, allergic lung inflammation was induced in pregnant dams via aerosol allergen challenge (sham, CAS or OVA). After weaning, pups were subjected to an experimental asthma protocol using OVA. Asn-297 IgG glycosylation was analysed in maternal and offspring serum. When mothers and offspring were sensitized to the same allergen (OVA-OVA), offspring had more severe experimental asthma. This was evidenced by altered antibody concentrations, increased bronchoalveolar lavage inflammatory cell influx and decreased lung tissue and lung draining lymph node regulatory T cell percentages. When mothers and offspring were sensitized to different allergens (CAS-OVA), this phenotype was no longer observed. Additionally, maternal serum from allergic mothers had significantly higher levels of pro-inflammatory IgG1, shown by decreased galactosylation and sialylation at the Asn-297 glycosylation site. Similar glycosylation patterns were observed in the serum of adult allergic offspring from allergic mothers. We observed a strong association between maternal experimental asthma during pregnancy, increased offspring airway inflammation and pro-inflammatory IgG glycosylation patterns in mothers and offspring. IgG glycosylation is not a standard measurement in the clinical setting, and we argue that it may be an important parameter to include in future clinical studies.
Highlights
Asthma is a chronic obstructive airway disease characterized by airway inflammation and hyperreactivity leading to recurring episodes of respiratory symptoms including cough and shortness of breath
This imbalance of Immunoglobulin G (IgG) glycosylation can be therapeutically compensated by administration of high dose intravenous immunoglobulin (IVIG), which leads to an increase in anti-inflammatory sialylated antibodies.[17]
We further show that these maternal IgG antibody glycosylation patterns persisted in adult allergic offspring and were associated with increased inflammatory responses in offspring experimental asthma
Summary
Asthma is a chronic obstructive airway disease characterized by airway inflammation and hyperreactivity leading to recurring episodes of respiratory symptoms including cough and shortness of breath. Transfer of maternal immunoglobulin G (IgG) antibodies protects the offspring from pathogens, while the humoral immune response is still inefficient. In autoimmune diseases, exacerbations are characterized by an increased frequency of agalactosylated IgG (G0) and a decreased frequency of sialic acid.[14,15,16] This imbalance of IgG glycosylation can be therapeutically compensated by administration of high dose intravenous immunoglobulin (IVIG), which leads to an increase in anti-inflammatory sialylated antibodies.[17] Importantly, in allergen-specific. Upon transfer to the fetus or neonate, these pro- or anti-inflammatory signals could strongly influence immune system development and predispose the offspring to inflammation or allergy susceptibility. We demonstrate that asthma exacerbation during pregnancy alters maternal serum IgG1 and IgG3 glycosylation patterns towards a pro-inflammatory phenotype. We further show that these maternal IgG antibody glycosylation patterns persisted in adult allergic offspring and were associated with increased inflammatory responses in offspring experimental asthma
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