Abstract
Cofactors may explain why in some cases food ingestion leads to anaphylaxis while in others elicits a milder reaction or tolerance. With cofactors, reactions become more severe and/or have a lower allergen threshold. Cofactors are present in up to 58% of food anaphylaxis (FAn). Exercise, NSAIDs, and alcohol are the most frequently described, although the underlying mechanisms are poorly known. Several hypotheses have suggested the influence of these cofactors on basophils and mast cells (MCs). Exercise has been suggested to enhance MC activation by increasing plasma osmolarity, redistributing blood flow, and activating adenosine and eicosanoid metabolism. NSAIDs’ cofactor effect has been related with cyclooxygenase inhibition and therefore, prostaglandin E2 (PGE2) production. Indeed, overexpression of adenosine receptor 3 (A3) gene has been described in NSAID-dependent FAn; A3 activation potentiates FcϵRI-induced MC degranulation. Finally, alcohol has been related with an increase of histamine levels by inhibition of diamino oxidase (DAO) and also with and increase of extracellular adenosine by inhibition of its uptake. However, most of these mechanisms have limited evidence, and further studies are urgently needed. In conclusion, the study of the immune-related mechanisms involved in food allergic reactions enhanced by cofactors is of the utmost interest. This knowledge will help to design both tailored treatments and prophylactic strategies that, nowadays, are non-existent.
Highlights
Food allergy is the main cause of anaphylaxis in children and in some series, in adults [1]
Other suggested mechanisms are related with the direct effect of exercise on basophils and mast cells (MCs) by modifying the cell count and histamine release (HR), redistributing the blood flow and increasing plasma osmolarity
Adenosine metabolism related genes were differentially expressed only in FDNIA. These findings suggest that [1] eicosanoid metabolism may play a role in the development of any anaphylaxis; [2] Non-steroidal anti-inflammatory drugs (NSAIDs) may have a universal synergistic effect in any food allergic patient; [3] the right amount of allergen may induce an anaphylaxis in FDNIA even in the absence of a cofactor; and [4] there are other yet to be confirmed mechanisms that explain the differences between NSAIDdependent and -independent food anaphylaxis (FAn)
Summary
Alcohol has been related with an increase of histamine levels by inhibition of diamino oxidase (DAO) and with and increase of extracellular adenosine by inhibition of its uptake. Most of these mechanisms have limited evidence, and further studies are urgently needed. The study of the immunerelated mechanisms involved in food allergic reactions enhanced by cofactors is of the utmost interest. This knowledge will help to design both tailored treatments and prophylactic strategies that, nowadays, are non-existent
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