Mast cells are hematopoietic tissue immune cells that secrete pre-stored mediators, such as histamine and tryptase, as well as, numerous de novo synthesized chemokines and cytokines in response to allergic or non-immune triggers.

The best-characterized mechanism of mast cell activation is antigen-mediated cross-linking of IgE bound to FcεRI on mast cells. Mast cells are indispensable for the development of allergic reactions, through cross-linking of their surface receptors for IgE (FcεRI), leading to degranulation and the release of vasoactive, pro-inflammatory, and nociceptive mediators. There is strong evidence that antigen-, IgE- and FcεRI-dependent activation of mast cell mediator secretion can influence the pathology of allergic disorders and that the consequences of this process can either directly affect structural cells residing in the affected tissues or influence the pathology indirectly through effects of mast cells on dendritic cells, T cells, B cells and other hematopoietic cell types.

In addition, a large number of IgE-independent modes of mast cell activation have been described.  Human mast cells express a multiplicity of G-protein-coupled receptors and other recognition sites on their surface which are involved in mast cell activation under physiological and pathophysiological conditions.  Stimulation of these receptors can either result in potentiation of FcεRI-mediated mast cell activation or induction of mast cell activation by themselves using different intracellular complementary, as well as, converging signaling pathways. Recently, the mast cell receptor MRGPRX2 has been identified as a cause of systemic pseudo-allergic reactions associated with, for example, the intake of drugs, foods and chemicals.

Although many therapies targeting IgE-specific allergies are available, such as anti-histamines, the prevalence of allergies and hypersensitivity is increasing, for example towards foods, drugs and environmental influences, with an urgent need to treat non-IgE-mediated allergic reactions, but also IgE-specific allergies more effectively.

The global prevalence for IgE-specific and non-IgE-mediated allergies has been rising to about 15% resulting in a tremendously large patient population.