Anaphylaxis is a systemic hypersensitivity reaction that can be life threatening. Mechanistically, it results from the immune activation and release of a variety of mediators that give rise to the signs and symptoms of this pathological event. For years, most of the research in anaphylaxis has focused on the contribution of the immune component. However, approaches that shed light on the participation of other cellular and molecular agents are necessary. Among them, the vascular niche receives the various signals (e.g., histamine) that elicit the range of anaphylactic events. Cardiovascular manifestations such as increased vascular permeability, vasodilation, hypotension, vasoconstriction, and cardiac alterations are crucial in the pathophysiology of anaphylaxis and are highly involved to the development of the most severe cases. Specifically, the endothelium, vascular smooth muscle cells, and their molecular signaling outcomes play an essential role downstream of the immune reaction. Therefore, in this review, we synthesized the vascular changes observed during anaphylaxis as well as its cellular and molecular components. As the risk of anaphylaxis exists both in clinical procedures and in routine life, increasing our knowledge of the vascular physiology and their molecular mechanism will enable us to improve the clinical management and how to treat or prevent anaphylaxis.Key MessageAnaphylaxis, the most severe allergic reaction, involves a variety of immune and non-immune molecular signals that give rise to its pathophysiological manifestations. Importantly, the vascular system is engaged in processes relevant to anaphylactic events such as increased vascular permeability, vasodilation, hypotension, vasoconstriction, and decreased cardiac output. The novelty of this review focuses on the fact that new studies will greatly improve the understanding of anaphylaxis when viewed from a vascular molecular angle and specifically from the endothelium. This knowledge will improve therapeutic options to treat or prevent anaphylaxis.

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Anaphylaxis is a life-threatening systemic hypersensitivity reaction. During anaphylaxis, mediator release by effector cells causes endothelial barrier breakdown, increasing vascular permeability and leakage of fluids, which may lead to tissue edema. Although endothelial cells (ECs) are key players in this context, scant attention has been paid to the molecular analysis of the vascular system, and further analyses of this cell type are necessary, especially in humans. The protein expression pattern of human microvascular ECs was analyzed in response to sera from anaphylactic patients (EC-anaphylaxis) and sera from non-allergic subjects (EC-control) after 2 hours of contact. Firstly, a differential quantitative proteomic analysis of the protein extracts was performed by mass spectrometry using an isobaric labeling method. Second, the coordinated behavior of the identified proteins was analyzed using systems biology analysis (SBA). The proteome of the EC-anaphylaxis system showed 7,707 proteins, of which 1,069 were found to be significantly altered between the EC-control and EC-anaphylaxis groups (p-value < 0.05). Among them, a subproteome of 47 proteins presented a high rate of change (|ΔZq| ≥ 3). This panel offers an endothelial snapshot of the anaphylactic reaction. Those proteins with the highest individual changes in abundance were hemoglobin subunits and structural support proteins. The interacting network analysis of this altered subproteome revealed that the coagulation and complement systems are the main biological processes altered in the EC-anaphylactic system. The comprehensive SBA resulted in 5,512 functional subcategories (biological processes), 57 of which were significantly altered between EC-control and EC-anaphylaxis. The complement system, once again, was observed as the main process altered in the EC system created with serum from anaphylactic patients. Findings of the current study further our understanding of the underlying pathophysiological mechanisms operating in anaphylactic reactions. New target proteins and relevant signaling pathways operating in the in vitro endothelial-serum system have been identified. Interestingly, our results offer a protein overview of the micro-EC-anaphylaxis environment. The relevance of the coagulation, fibrinolytic, contact and complement systems in human anaphylaxis is described. Additionally, the untargeted high-throughput analysis used here is a novel approach that reveals new pathways in the study of the endothelial niche in anaphylaxis.

Introduction: Allergy to nonspecific lipid transfer protein (nsLTP) is the main cause of plant-food allergy in Spain. nsLTPs are widely distributed in the plant kingdom and have high cross-reactivity but extremely variable clinical expression. Little is known about the natural evolution of this allergy, which complicates management. The objective of this study was to assess the development of allergy to new plant foods in nsLTP-sensitized patients 10 years after diagnosis. Methods: One hundred fifty-one patients showing specific IgE to nsLTP determined by ISAC (Thermofisher) were included. After clinical workup (i.e., anamnesis, skin test, and challenge when needed), these patients were divided into two groups: 113 patients allergic to one or more plant food (74.5%) and 38 patients not allergic to any plant food (25.1%). Ten years later, a telephone interview was conducted to check whether patients had developed additional allergic reactions to plant foods. Results: Ten years after diagnosis, 35 of the 113 (31%) plant-food-allergic patients sensitized to nsLTP reported reactions to new, previously tolerated plant foods, mainly Rosaceae/Prunoideae fruits and nuts followed by vegetables, Rosacea/Pomoideae fruits, legumes, and cereals. Five out of 38 (13.2%) patients previously sensitized to nsLTP but without allergy to any plant food had experienced allergic reactions to some plant food: two to Rosaceae/Prunoideae fruits, two to Rosaceae/Prunoideae fruit and nuts, and one to legumes. Conclusion: Patients sensitized to nsLTP developed allergic reactions to other plant foods, mainly Rosaceae-Prunoideae fruits and nuts. This was more frequent among plant-food-allergic patients than among those who had never had plant-food allergy.