{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T23:24:28Z","timestamp":1792625068554,"version":"4.5.0"},"reference-count":67,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,2,17]],"date-time":"2021-02-17T00:00:00Z","timestamp":1613520000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    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\u2019 cofactor effect has been related with cyclooxygenase inhibition and therefore, prostaglandin E\n                    <jats:sub>2<\/jats:sub>\n                    (PGE\n                    <jats:sub>2<\/jats:sub>\n                    ) production. Indeed, overexpression of adenosine receptor 3 (A\n                    <jats:sub>3<\/jats:sub>\n                    ) gene has been described in NSAID-dependent FAn; A\n                    <jats:sub>3<\/jats:sub>\n                    activation potentiates Fc\n                    <jats:italic>\u03f5<\/jats:italic>\n                    RI-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.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2020.623071","type":"journal-article","created":{"date-parts":[[2021,2,19]],"date-time":"2021-02-19T16:27:52Z","timestamp":1613752072000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":32,"title":["Immune-Mediated Mechanisms in Cofactor-Dependent Food Allergy and Anaphylaxis: Effect of Cofactors in Basophils and Mast Cells"],"prefix":"10.3389","volume":"11","author":[{"given":"Rosa","family":"Mu\u00f1oz-Cano","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"San Bartolome","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roc\u00edo","family":"Casas-Saucedo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Araujo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Gelis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Ruano-Zaragoza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordi","family":"Roca-Ferrer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis","family":"Palomares","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarita","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan","family":"Bartra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariona","family":"Pascal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,2,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1016\/j.jaip.2014.07.007","article-title":"Prevalence and characteristics of adult-onset food allergy","volume":"3","author":"Kamdar","year":"2015","journal-title":"J Allergy Clin Immunol Pract"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1111\/all.12437","article-title":"Anaphylaxis: guidelines from the European Academy of Allergy and Clinical Immunology","volume":"69","author":"Muraro","year":"2014","journal-title":"Allergy"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1111\/all.12193","article-title":"About the role and underlying mechanisms of cofactors in anaphylaxis","volume":"68","author":"W\u00f6lbing","year":"2013","journal-title":"Allergy Eur J Allergy Clin Immunol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1111\/all.13380","article-title":"Factors increasing the risk for a severe reaction in anaphylaxis: An analysis of data from The European Anaphylaxis Registry","volume":"73","author":"Worm","year":"2018","journal-title":"Allergy"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1111\/all.12475","article-title":"First European data from the network of severe allergic reactions (NORA)","volume":"69","author":"Worm","year":"2014","journal-title":"Allergy"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1111\/all.12272","article-title":"The epidemiology of anaphylaxis in Europe: A systematic review","volume":"68","author":"Panesar","year":"2013","journal-title":"Allergy"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2012.02877.x.","article-title":"Co-factor-enhanced food allergy","volume":"67","author":"Cardona","year":"2012","journal-title":"Allergy"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1111\/all.13207","article-title":"Patterns of anaphylaxis after diagnostic workup: A follow-up study of 226 patients with suspected anaphylaxis","volume":"72","author":"Oropeza","year":"2017","journal-title":"Allergy"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1111\/all.12677","article-title":"Pathophysiological mechanisms of exercise-induced anaphylaxis: an EAACI position statement","volume":"70","author":"Ansley","year":"2015","journal-title":"Allergy"},{"key":"B10","doi-asserted-by":"publisher","first-page":"S91","DOI":"10.1055\/s-2007-972705","article-title":"Exercise immunology: practical applications","volume":"18","author":"Nieman","year":"1997","journal-title":"Int J Sports Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1136\/thx.38.10.771","article-title":"1983 U. 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