Differential Metabolites Before and After Allergen Specific Immunotherapy in Children with Allergic Asthma

Yinyan Yue,* Menghong Sang,* Shuyan Zhang, Shengang Hu, Yinan Zhang, Suqin Zhang Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Suqin Zhang, Email [email protected]: Asthma is the most common chronic respiratory disease in children. Although conventional treatments such as inhaled corticosteroids and long-acting β 2-receptor agonists can effectively control symptoms, some children still face the problem of frequent attacks and drug side effects. As a potential etiological treatment, allergen-specific immunotherapy (AIT) aims to induce immune tolerance by gradually increasing exposure to specific allergens, thereby relieving asthma symptoms in the long term. This study aimed to investigate the differential metabolites in children with allergic asthma before and after subcutaneous allergen-specific immunotherapy (SCIT) using a non-targeted metabolomics approach, to gain deeper insight into the potential mechanisms of AIT and its systemic effects.Methods: A total of 30 children were enrolled, including 15 healthy controls and 15 children with asthma (prior to AIT and after one year of AIT). Serum samples were analyzed using LC-MS to identify differential metabolites and their associated metabolic pathways.Results: AIT could reverse the lung function of patients with allergic asthma. There were six pathways that had difference among the control group, pre-AIT group and post-AIT group. These six pathways were the PPAR signaling pathway (impact = 0.6000), the GABAergic synapse (impact =0.5882), the alanine, aspartate and glutamate metabolism (impact =0.4290), the central carbon metabolism in cancer (impact =0.3019), the arginine biosynthesis (impact =0.2956) and the linoleic acid metabolism (impact =0.2368). There were 24 metabolites that had difference among these three groups. During them, there were 5 metabolites (9,12,13-TriHOME; 9,10-Epoxyoctadecenoic acid; Isocitrate; L-Arginine; Succinic acid semialdehyde) of the pre-AIT patients reversed by AIT compared to the control group. The levels of the 5 metabolites were increased of the pre-AIT compared to the control group. After one year of usage of AIT, the levels of the 5 metabolites were decreased. Comparing of the pre-AIT group and post-AIT group revealed additional pathways: the intestinal immune network for IgA production (impact = 0.5) and aldosterone-regulated sodium reabsorption (impact = 0.4). Key metabolites included all-trans-retinoic acid, cortisol, and cortisone.Conclusion: This study demonstrates for the first time the impact of one-year AIT on the metabolic profile of children with allergic asthma receiving long-term inhaled glucocorticoid therapy. Children with asthma mainly exhibited six pathways which including 24 metabolites disturbances compared to healthy peers, 5 of which were reversed following AIT. AIT may synergistically enhance the therapeutic effects of glucocorticoids while also introducing novel regulatory mechanisms. The persistence of these metabolic changes over a one-year period supports their validity as stable therapeutic outcomes rather than transient fluctuations. Keywords: allergen specific immunotherapy, metabolite, allergic asthma, GABAergic synapse, inhaled-glucocorticoid