The current definition of an immediate hypersensitivity reaction (IHSR) involves anaphylactic type clinical manifestations that occur within the first one (to six) hour(s) after exposure to a trigger. The most common triggers that can induce immediate reactions are drugs, food, venom and latex. The pathophysiology of IHSR involves the activation and degranulation of mast cells and basophils. Those cells release mediators, such as histamine, lipid metabolytes, cytokines and proteases. This leads to vasodilation, increased vascular permeability and smooth muscle contraction. Both mast cells and basophils can be activated by immunological and non-immunological mechanisms.
Mast cells are components of the innate immune system and are considered the major effector cells of IHSRs. Immunological IHSRs, (also named type I hypersensitivity reactions), are antigen specific and IgE mediated. Mast cells are activated through exposure to an allergen that cross-links allergen-specific IgE, if this is already bound to the high-affinity Fc epsilon receptor 1 (FceRI) on the cell surface.
Alternatively, mast cells can be activated and degranulated after non-specific (non-immunological) mechanisms, including anaphylatoxins (C3a and C5a), physical stimuli (pressure and temperature changes), infections, cytokines and neuropeptides. Moreover, mast cells can be activated after inhibition of cyclooxygenase-1 by nonsteroidal anti-inflammatory drugs (NSAIDs), that are major triggers of urticaria, angioedema and anaphylaxis. Furthermore, a novel mechanism was recently described to explain some nonallergic anaphylactic reactions. Cationic substances, acting as basic secretagogues activate mouse mast cells in vitro and in vivo through a single receptor, the Mrgprb2, which is an ortholog of the human MAS-related G protein-coupled receptor-X2 (MRGPRX2). Several basic exogenous substances are involved in MRGPRX2-mediated mast cell activation, based on in vitro studies. Neuromuscular blocking agents and all fluoroquinolones have a tetrahydroisoquinoline motif, which can bind and activate this receptor. Compound 48/80, vespid mastoparan, opioids and icatibant are other examples of agonists of MRGPRX2. Targeting human MRGPRX2 is a promising way to prevent or treat nonallergic drug hypersensitive reactions and other inflammatory diseases. Finally, other drugs, as vancomycin and iodinated contrast media, can activate mast cells by mechanisms not completely elucidated.
In this Research Topic, we aim to present a collection of manuscripts evaluating mechanisms of allergic and nonallergic immediate hypersensitivity reactions that would involve mast cell activation. We welcome studies regarding mast cell activation triggered by drugs, food, venom, and even mast cell activation disorders, such as mastocytosis and mast cell activation syndromes. Those studies could incorporate Original Research, Method, Mini Review and Case Report articles, focusing on, but not limited to, the following subtopics:
• Anaphylaxis induced by any trigger
• Drug-induced immediate hypersensitivity reactions
• Food and venom-induced immediate hypersensitivity reactions
• Urticaria and angioedema
• Mastocytosis and mast cell activation syndromes
• Immunologic and nonimmunologic mechanisms of mast cell activation
• Desensitization and induction of mast cell tolerance
• Novel immunological assays for measuring mast cell activation/degranulation
• Animal models of mast cell activation
Prof. Castells is the Principal Investigator for the PIONEER Bluprint Clinical Study on Indolent Systemic Mastocytosis. The other Topic Editors declare no competings interest in relation to this topic.
The current definition of an immediate hypersensitivity reaction (IHSR) involves anaphylactic type clinical manifestations that occur within the first one (to six) hour(s) after exposure to a trigger. The most common triggers that can induce immediate reactions are drugs, food, venom and latex. The pathophysiology of IHSR involves the activation and degranulation of mast cells and basophils. Those cells release mediators, such as histamine, lipid metabolytes, cytokines and proteases. This leads to vasodilation, increased vascular permeability and smooth muscle contraction. Both mast cells and basophils can be activated by immunological and non-immunological mechanisms.
Mast cells are components of the innate immune system and are considered the major effector cells of IHSRs. Immunological IHSRs, (also named type I hypersensitivity reactions), are antigen specific and IgE mediated. Mast cells are activated through exposure to an allergen that cross-links allergen-specific IgE, if this is already bound to the high-affinity Fc epsilon receptor 1 (FceRI) on the cell surface.
Alternatively, mast cells can be activated and degranulated after non-specific (non-immunological) mechanisms, including anaphylatoxins (C3a and C5a), physical stimuli (pressure and temperature changes), infections, cytokines and neuropeptides. Moreover, mast cells can be activated after inhibition of cyclooxygenase-1 by nonsteroidal anti-inflammatory drugs (NSAIDs), that are major triggers of urticaria, angioedema and anaphylaxis. Furthermore, a novel mechanism was recently described to explain some nonallergic anaphylactic reactions. Cationic substances, acting as basic secretagogues activate mouse mast cells in vitro and in vivo through a single receptor, the Mrgprb2, which is an ortholog of the human MAS-related G protein-coupled receptor-X2 (MRGPRX2). Several basic exogenous substances are involved in MRGPRX2-mediated mast cell activation, based on in vitro studies. Neuromuscular blocking agents and all fluoroquinolones have a tetrahydroisoquinoline motif, which can bind and activate this receptor. Compound 48/80, vespid mastoparan, opioids and icatibant are other examples of agonists of MRGPRX2. Targeting human MRGPRX2 is a promising way to prevent or treat nonallergic drug hypersensitive reactions and other inflammatory diseases. Finally, other drugs, as vancomycin and iodinated contrast media, can activate mast cells by mechanisms not completely elucidated.
In this Research Topic, we aim to present a collection of manuscripts evaluating mechanisms of allergic and nonallergic immediate hypersensitivity reactions that would involve mast cell activation. We welcome studies regarding mast cell activation triggered by drugs, food, venom, and even mast cell activation disorders, such as mastocytosis and mast cell activation syndromes. Those studies could incorporate Original Research, Method, Mini Review and Case Report articles, focusing on, but not limited to, the following subtopics:
• Anaphylaxis induced by any trigger
• Drug-induced immediate hypersensitivity reactions
• Food and venom-induced immediate hypersensitivity reactions
• Urticaria and angioedema
• Mastocytosis and mast cell activation syndromes
• Immunologic and nonimmunologic mechanisms of mast cell activation
• Desensitization and induction of mast cell tolerance
• Novel immunological assays for measuring mast cell activation/degranulation
• Animal models of mast cell activation
Prof. Castells is the Principal Investigator for the PIONEER Bluprint Clinical Study on Indolent Systemic Mastocytosis. The other Topic Editors declare no competings interest in relation to this topic.