Multi-omics Analysis Points to Altered Platelet Functions in Severe Food-Associated Respiratory Allergy.

Abstract

Background: Prevalence and severity of allergic diseases have increased worldwide. To date, respiratory allergy phenotypes are not fully characterized and, along with inflammation progression, treatment is increasingly complex and expensive. Profilin sensitization constitutes a good model to study the progression of allergic inflammation. Our aim was to identify the underlying mechanisms and the associated biomarkers of this progression, focusing on severe phenotypes, using transcriptomics and metabolomics. Methods: 25 subjects were included in the study. Plasma samples were analyzed using Gas and Liquid Chromatography coupled to Mass Spectrometry (GC -MS and LC -MS, respectively). Individuals were classified in 4 groups – “non -allergic”, “mild”, “moderate” and “severe” – based on their clinical history, their response to an oral challenge test with profilin , and after a refinement using a mathematical metabolomic model. PBMCs were used for microarray analysis. Results: We found a set of transcripts and metabolites that were specific for the “severe” phenotype. By metabolomics, it was detected a decrease in carbohydrate s and pyruvate and an increase in lactate , suggesting aerobic glycolysis. Ohter metabolites were incremented in severe group: lysophospholipids, sphingosine - 1 -phosphate, sphinganine - 1 -phosphate, as well as lauric, myristic, palmitic, and oleic fatty acids. On the other hand, carnitines were decreased along severity. Significant transcripts in the “severe” group were downregulated and were associated to platelet functions, protein synthesis, histone modification and fatty acid metabolism. Conclusions: We have found evidence that points to the association of severe allergic inflammation with platelet functions alteration, together with reduced protein synthesis, and switch of immune cells to aerobic glycolysis.