Immune-Mediated Mechanisms in Cofactor-Dependent Food Allergy and Anaphylaxis: Effect of Cofactors in Basophils and Mast Cells

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.

Advances in the understanding of the cofactor effect in lipid transfer protein food allergy: From phenotype description to clinical management

“…Female predominance in the CG may be related to hormone factors; estrogen levels have been related to higher risk of anaphylaxis. 2 Indeed, NSAID intake to control menstrual pain is a frequent practice that may explain the frequent involvement of these drugs in our series.…”

“…To the Editor, Cofactors may explain why in some cases food ingestion leads to anaphylaxis while in others elicits a milder reaction/tolerance. 1,2 Cofactors have also been related to a complex food allergy (FA) phenotype such as Lipid Transfer Protein (LTP)-FA, 3 although limited data regarding the epidemiology and clinical profile of these patients are available.…”

Associations between food-specific IgG and health outcomes in an asymptomatic physical examination cohort

“…Acute food allergy and chronic food allergy are correlated with a set of co-factors [ 31 ]. However, the diagnosis of food allergy is a clinical challenge and requires history inquiry and food exclusion in most cases [ 32 , 33 ].…”

Effects of Food-Specific IgG on Health Outcomes of Asymptomatic Physical Examination Population

“…As we know, acute food allergy and chronic food allergy are mainly related with some co-factors [30]. In fact, the diagnosis of food allergy is a clinical challenge and requires history inquiry and food exclusion in most cases [31,32], and it is very difficult to make in patients without apparent symptoms.…”