Frontiers in Immunology (Feb 2021)

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

  • Rosa Muñoz-Cano,
  • Rosa Muñoz-Cano,
  • Rosa Muñoz-Cano,
  • Rosa Muñoz-Cano,
  • Clara San Bartolome,
  • Clara San Bartolome,
  • Clara San Bartolome,
  • Rocío Casas-Saucedo,
  • Rocío Casas-Saucedo,
  • Rocío Casas-Saucedo,
  • Giovanna Araujo,
  • Giovanna Araujo,
  • Sonia Gelis,
  • Sonia Gelis,
  • Maria Ruano-Zaragoza,
  • Maria Ruano-Zaragoza,
  • Maria Ruano-Zaragoza,
  • Jordi Roca-Ferrer,
  • Jordi Roca-Ferrer,
  • Jordi Roca-Ferrer,
  • Francis Palomares,
  • Francis Palomares,
  • Margarita Martin,
  • Margarita Martin,
  • Margarita Martin,
  • Joan Bartra,
  • Joan Bartra,
  • Joan Bartra,
  • Joan Bartra,
  • Mariona Pascal,
  • Mariona Pascal,
  • Mariona Pascal

DOI
https://doi.org/10.3389/fimmu.2020.623071
Journal volume & issue
Vol. 11

Abstract

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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.

Keywords