The search for severity predictive biomarkers in food allergy: from literature review to experimental setup

Abstract

In food allergy, the immune system mistakenly identifies specific food proteins as harmful, initiating an immune response. A skewed Th2 profile characterizes these immune responses. Th2 cells are a major player in the cytokine secretion of IL-4, IL-5 and IL-13. These cytokines increase 1 the differentiation of naïve T cells to Th2 cells and stimulate B cells to produce IgE towards the allergens. TH2A cells are an allergen-specific Th2 subset that has increased cytokine secretion and are thought to be only present in atopic individuals. In addition, Tfh13, a Tfh cell subset, has increased IL-13 secretion and is believed to be responsible for producing high-affinity anaphylactic IgE against allergens. For these cells, a flow cytometric panel was designed to identify these cells in PBMCs. An essential aspect of the immune system is the chemotaxis of immune cells through the body. We developed a panel for a flow cytometric analysis of T cells homing toward skin, lung, and gut tissue. The designed panels were tested on healthy donor PBMCs. The activation of the PBMCs in the homing panel tests showed that more prolonged stimulation (as well as stimulation with a higher concentration of stimuli) showed increased homing phenotypes in lung and gut homing tissues. In addition, the BAT was correlated to its ability to correctly predict the outcome of an oral food challenge (OFC). This study showed that BAT is better at predicting a positive outcome of the OFC for patients with more severe symptoms (82%). More false results were given with less severe or tolerant clinical outcomes (9% false positive and 9% false negative).