Asthma is a common chronic inflammatory disease. Pathogenic mechanism underlying asthma is complex. The inflammatory response of asthma includes lymphocytes (T, B cells), ILC2, eosinophils and other types of immune and inflammatory cells. T CD4+ T helper 2 cells (Th2 cells) are thought to play a central role in regulating the phenotype of allergic asthma. Asthma is often closely associated with Th1/Th2 cell imbalance. Non-coding RNAs (ncRNAs) are non-protein coding RNA molecules in the transcriptome, mainly including microRNAs (miRNAs), long non-coding RNAs and circRNAs, etc., which are widely found in eukaryotic transcriptome and participate in the regulation of a variety of biological processes. ncRNAs are considered to function as modulators of the immune system. Their biological changes represent an important mechanism for the development of immune-mediated diseases. This chapter mainly discusses the epigenetic regulation of Th2 cells and their cytokines in asthma by non-coding RNAs. It helps us to better understand the pathogenesis of asthma and find potential asthma biomarkers.

Allergen-specific immunotherapy (AIT) is the only disease-modifying treatment for allergic rhinitis and asthma, but objective biomarkers for monitoring immune tolerance and predicting adverse reactions remain lacking. ImmunoglobulinG (IgG) glycosylation has been validated as an effective biomarker in numerous inflammatory diseases. This study aimed to explore plasma IgG N-glycan dynamics as predictive markers for AIT tolerance and adverse events. We enrolled 37 patients with allergic asthma or rhinitis undergoing subcutaneous AIT, 26 patients were longitudinally sampled at three time points: pre-treatment, maintenance initiation, and after more than 6 months of maintenance therapy. IgG N-glycans were analyzed by ultra-performance liquid chromatography (UPLC). Longitudinal analysis showed total IgG galactosylation and sialylation gradually increased, while bisecting glycans decreased during AIT. Among 37 patients, those with adverse reactions exhibited significantly elevated GP6, reduced GP18, GP23, lower galactosylation and sialylation, and increased bisecting glycans at baseline compared with tolerant patients. Receiver operating characteristic (ROC) curve analysis revealed that the combined glycan model achieved an area under the curve (AUC) of 0.863 for adverse reaction prediction. These findings demonstrate that IgG N-glycosylation remodeling correlates with AIT progression and can serve as a potential pretreatment biomarker for risk stratification. Plasma IgG N-glycan profiling provides a minimally invasive, mechanism-based tool to improve AIT safety and efficacy, which deserves further multicenter validation.

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.