{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T10:18:17Z","timestamp":1788257897488,"version":"build-2803163510"},"reference-count":47,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Anaphylaxis is a severe systemic hypersensitivity reaction characterized by rapid onset, unpredictable clinical course, and potentially fatal outcomes. Although its diagnosis remains primarily clinical, the identification of biomarkers capable of improving risk stratification and understanding disease mechanisms remains an important unmet need. Among the mediators implicated in anaphylaxis, platelet-activating factor (PAF) has emerged as a key effector molecule involved in vascular permeability, bronchoconstriction, platelet activation, and cardiovascular dysfunction. The biological activity of PAF is tightly regulated by platelet-activating factor acetylhydrolase (PAF-AH), the enzyme responsible for its degradation, making the PAF\u2013PAF-AH axis a potentially important determinant of reaction severity. OBJECTIVES: The present review summarizes current knowledge regarding the biology of PAF and PAF-AH and examines their role in the pathophysiology of anaphylaxis, with particular emphasis on Hymenoptera venom allergy (HVA). The therapeutic potential of targeting the PAF pathway is also discussed. Experimental and clinical evidence consistently suggests an association between increased PAF activity, reduced PAF-AH activity, and more severe anaphylactic reactions. However, methodological limitations, biological variability, and conflicting findings across studies currently limit the clinical applicability of these molecules as standalone biomarkers. Overall, the PAF\u2013PAF-AH axis represents a biologically plausible link between molecular mechanisms and clinical severity in anaphylaxis. Further studies are required to standardize measurements, validate clinical utility, and define the role of this pathway as both a biomarker and therapeutic target; hence gaining insight into PAF\u2019s role in various biological processes is critical.<\/jats:p>","DOI":"10.3390\/ijms27177783","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T09:48:36Z","timestamp":1788256116000},"page":"7783","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Platelet Activating Factor\u2013Platelet Activating Factor Acetylhydrolase Enzyme Axis in Anaphylaxis: Current Evidence and Future Perspectives"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2496-7932","authenticated-orcid":false,"given":"Arianna","family":"Vignini","sequence":"first","affiliation":[{"name":"Department of Clinical Sciences, Universit\u00e0 Politecnica delle Marche, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9452-8727","authenticated-orcid":false,"given":"Sabrina","family":"Costanzo","sequence":"additional","affiliation":[{"name":"Postgraduate School of Allergy and Clinical Immunology, Marche Polytechnic University, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9873-9695","authenticated-orcid":false,"given":"Matteo","family":"Martini","sequence":"additional","affiliation":[{"name":"Allergy Unit, Department of Internal Medicine, University Hospital AOU delle Marche, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonila","family":"Alia","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Universit\u00e0 Politecnica delle Marche, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1127-0801","authenticated-orcid":false,"given":"Valentina","family":"Membrino","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Universit\u00e0 Politecnica delle Marche, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiziana","family":"Di Crescenzo","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Universit\u00e0 Politecnica delle Marche, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Buti","sequence":"additional","affiliation":[{"name":"Postgraduate School of Allergy and Clinical Immunology, Marche Polytechnic University, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Beatrice","family":"Bil\u00f2","sequence":"additional","affiliation":[{"name":"Postgraduate School of Allergy and Clinical Immunology, Marche Polytechnic University, 60126 Ancona, Italy"},{"name":"Allergy Unit, Department of Internal Medicine, University Hospital AOU delle Marche, 60126 Ancona, Italy"},{"name":"Department of Clinical and Molecular Sciences, Marche Polytechnic University, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1016\/j.jaci.2020.01.017","article-title":"Anaphylaxis\u2014A 2020 practice parameter update, systematic review, and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) analysis","volume":"145","author":"Shaker","year":"2020","journal-title":"J. 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