D1.307 - Lipid metabolic remodeling in Food-induced anaphylaxis revealed by integrated proteomic and lipidomic analyses

Food-induced anaphylaxis (FIA) is a severe, rapidly progressing allergic reaction with increasing prevalence worldwide. Lipid metabolism has emerged as key modulator of inflammation and immune responses, yet its role in anaphylaxis remains unexplored. Investigating these molecular pathways may uncover novel biomarkers and therapeutic targets for better diagnosis and management of food allergies.

A murine model of FIA was established using Pru p 3, a major peach allergen. Mice were sensitized over six weeks with Pru p 3 and its lipid ligand as an adjuvant. In the eighth week, mice were challenged, and 15 minutes post-challenge, animals from three groups — control, sensitized, and challenged — were sacrificed for sample collection. Blood was drawn to obtain plasma and livers were extracted for further analysis. The lipid profile of plasma samples was assessed using a Cobas 6000 autoanalyzer. Proteomic profiling of plasma was performed using Tandem Mass Tag-based quantitative mass spectrometry. In parallel, targeted metabolomic analysis of liver samples was conducted using liquid chromatography-mass spectrometry. Data were analyzed using statistical tests with significance set at p < 0.05.

The proteomic profiling of plasma revealed significant differences in anaphylactic mice. Specifically, 78 proteins were found significantly altered between anaphylactic and control mice, and 75 between sensitized and anaphylactic mice. The study of the functional categories of plasma proteins also showed a total of 110 categories altered between anaphylactic and control and sensitized mice. Specifically, one of the main altered categories was cholesterol metabolism. Following this, plasma analysis of cholesterol metabolism components showed a significant reduction in HDL-C in anaphylaxis. On the other hand, lipidomic analysis of the livers showed that triglycerides, phosphatidylcholines and fatty acids were the main lipid groups affected. Specifically, phosphatidylinositols were altered exclusively in sensitized mice, while ceramides, triglycerides, cholesterol, and phosphatidylethanolamines were mostly altered in anaphylactic mice.

Our findings highlight the involvement of specific lipid metabolism in FIA. The alterations observed in HDL levels and liver lipid composition suggest a systemic metabolic response related to cholesterol in anaphylaxis. These results provide novel insights into the molecular mechanisms of FIA and may contribute to the identification of new diagnostic or therapeutic targets.