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Role of myeloid cells, their mediators and their antibody receptors in allergic shock (anaphylaxis) using humanized mouse models and clinical samples

Final Report Summary - MYELOSHOCK (Role of myeloid cells, their mediators and their antibody receptors in allergic shock (anaphylaxis) using humanized mouse models and clinical samples)

Allergic shock (anaphylaxis) is a life-threatening reaction to allergens (food, drugs, pollens, venom, etc) occurring in individuals that produce particular antibodies against these allergens. Project MyeloSHOCK aimed at unraveling the parameters that control anaphylaxis using novel mouse models closer to the human physiology, strengthened by human-based studies involved patients undergoing anaphylaxis. We identified several pathways leading to disease induction depending on the type of antibodies that can bind the allergen. We have identified the predominant antibody receptors involved in anaphylaxis induction and severity in normal mice, but also in mice expressing human antibody receptors (as a correlate to human anaphylaxis), and could exclude antibody receptors that cannot participate in this reaction. A clinical study on anaphylaxis to drugs enabled us to confirm the findings in humans, describing a novel pathway of anaphylaxis based on IgG antibodies, neutrophils and their release of platelet-activating factor. This novel pathway may explain some of the “idiopathic” anaphylaxis reactions described in humans for which no “classical” pathway could be proposed. Through these analyses in mouse models and analyses using human samples, we increased the understanding of anaphylaxis and suggest novel treatment possibilities for this life-threatening reaction that has neither specific treatment nor cure.