Maternal Low-Dose Lipopolysaccharide Exposure and House Dust Mite Challenge Alter Serum IgG N-Glycosylation in...

Background: The "hygiene hypothesis" and "farm effect" suggest that early-life microbial exposure protects against allergic diseases. Maternal low-dose lipopolysaccharide (LPS) exposure during pregnancy attenuates allergic airway inflammation in offspring, yet the underlying mechanisms remain incompletely understood. Immunoglobulin G (IgG) N-glycosylation critically regulates antibody effector functions and maternal-fetal immune transfer, but its role in transgenerational allergy protection is unknown. Objective: To investigate whether maternal low-dose LPS exposure modulates serum IgG N-glycan profiles in offspring and whether these glycomic changes are associated with protection against house dust mite (HDM)-induced allergic airway inflammation. Methods: Pregnant C57BL/6J mice received intraperitoneal LPS (7 µg/kg) or phosphate-buffered saline (PBS) on gestational day 15. Offspring were sensitized with HDM extract or PBS at 6 weeks of age. Serum IgG was purified using Protein G affinity chromatography, and N-glycans were released with PNGase F, labeled with 2-aminobenzamide, and analyzed by ultra-performance liquid chromatography (UPLC) with fluorescence detection. Twelve glycan peaks (GP1-GP12) and five derived traits (galactosylation, sialylation, monogalactosylation, digalactosylation, and bisecting glycans) were quantified. Results: HDM challenge significantly altered offspring IgG glycosylation, characterized by decreased digalactosylation, total galactosylation, and sialylation, consistent with inflammatory glycan signatures reported in other inflammatory diseases. Maternal LPS exposure alone induced similar glycomic shifts in offspring (decreased digalactosylation, total galactosylation, and sialylation). In HDM-challenged offspring, maternal LPS pretreatment produced a trend toward reduced lung inflammation without statistical significance; however, IgG glycan differences between LPS-HDM and PBS-HDM groups were non-significant. Conclusions: Maternal low-dose LPS exposure reduced offspring IgG galactosylation and sialylation. HDM challenge produced similar glycomic changes. Despite a trend toward attenuation of HDM-induced lung inflammation, maternal LPS did not restore IgG glycosylation. These findings provide first evidence linking prenatal immune stimulation to transgenerational IgG glycomic remodeling.