Maternal asthma is associated with persistent changes in allergic offspring antibody glycosylation

Background: 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.

Objective: Using a mouse model, this study examined how maternal allergic airway inflammation during pregnancy influenced offspring IgG antibody glycosylation and experimental asthma severity. The effects of mothers/offspring having different allergies i.e. casein (CAS)/ovalbumin (OVA) or the same allergy (OVA/OVA) were tested.

Methods: Female mice were either sham sensitized, or sensitized to CAS or OVA before mating. Then, allergic lung inflammation was induced in pregnant dams via aerosol allergen challenge. After weaning, pups were subjected to an experimental asthma protocol using OVA. IgG glycosylation was analyzed in both maternal and allergic offspring serum.

Results: When mothers/offspring were sensitized to the same allergen (OVA), several aspects of offspring experimental asthma were more severe when compared to allergic offspring from sham treated mothers. This was evidenced by altered antibody concentrations, increased BAL inflammatory cell influx and decreased lung tissue and lymph node FoxP3 cell numbers. When mothers/offspring were sensitized to different allergens (CAS-OVA) this phenotype was no longer observed. Maternal serum from allergic mothers had significantly higher levels of pro-inflammatory IgG1, evidenced by decreased galactosylation and sialylation at the Asn-297 glycosylation site. These same patterns were reflected in the serum of adult allergic offspring.

Conclusions: IgG glycosylation patterns in offspring depend on maternal allergic airway inflammation and may contribute substantially to the establishment of the asthma phenotype.