2.    Allergy: Current and emerging biomarkers and therapeutic approaches
2.1.  Immune dysregulation
Allergic disease results from a Th2-biased immune response to environmental allergens in genetically predisposed atopic individuals. Trained immunity, characterized by innate immune cells displaying heightened reactivity and memory-like characteristics which occurs through transcriptomic, epigenetic, and metabolic reprograming following exposure to specific triggers, may play an important role in this context.13 Airway epithelium repetitively primed with Th1 (IFN-g) or Th2 (IL-4) cytokines present imprinted, polarized “Th1/Th2” gene networks. Human bronchial epithelial cells stimulated with IL-4, but not IFN-g, produced enhanced levels of IL-24. IL-24 was also increased in allergic rhinitis patients, demonstrating its potential as a biomarker of T2-polarized epithelium and allergic inflammation.14 Additionally, damaged epithelial barriers result in sensitization to different allergens due to alarmins that mature CD4+T-cells into Th2-cells and stimulate the overproduction of IL-4, IL-5, IL-9, IL-13 and IL-31. These cytokines promote the Th2-immune response, resulting in IgE isotype switching and involve mechanisms in chronic tissue remodelling during allergic conditions. These include mucus hypersecretion, vascular leakage, smooth muscle cell hypercontraction, neurogenesis, and angiogenesis.15,16 During sensitization, IgE binds to FcɛRI on mast cells (MCs) and basophils. Upon allergen exposure, the IgE-bound receptors aggregate, triggering immediate hypersensitivity reactions with various clinical manifestations affecting single or multiple organs with mild-moderate to severe symptoms including anaphylaxis (Figure 2).15,16 Allergic disorders are heterogeneous, with distinct phenotypes, genotypes and endotypes that differ in pathophysiology (Table 1).12
Figure 2: Overview of allergic inflammation: cellular and molecular mechanisms