{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T14:05:16Z","timestamp":1790258716011,"version":"4.1.0"},"reference-count":100,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Tryptase is the principal biomarker of mast cell (MC) burden and activation, routinely used in the diagnosis and management of MC-related disorders. Beyond its established role in confirming anaphylaxis, serum tryptase has gained increasing relevance in the diagnosis of systemic mastocytosis, hereditary \u03b1-tryptasemia (H\u03b1T), cutaneous mastocytosis, and selected haematologic diseases. Recent advances in MC biology, tryptase genetics, and disease classification have substantially improved the interpretation of baseline and acute (event-related) tryptase measurements. In particular, validation of the \u201c20% + 2\u201d consensus formula for MC activation and the recognition of H\u03b1T as a common genetic cause of elevated baseline serum tryptase have refined diagnostic algorithms and risk-stratification strategies. This review summarizes current knowledge on tryptase physiology, laboratory assessment, and clinical significance across multiple disease settings, with particular emphasis on the interpretation of baseline serum tryptase, the diagnostic role of tryptase in anaphylaxis and mastocytosis, and emerging applications in allergy, hematology, and chronic inflammatory disorders. Understanding both the strengths and limitations of serum tryptase measurement is essential for accurate diagnosis, prognostic assessment, and personalized patient management.<\/jats:p>","DOI":"10.3390\/biom16091360","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T09:01:38Z","timestamp":1789981298000},"page":"1360","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Understanding Tryptase Physiology, Clinical Significance, and Diagnostic Applications: Where Do We Stand?"],"prefix":"10.3390","volume":"16","author":[{"given":"Mara","family":"De Amici","sequence":"first","affiliation":[{"name":"Immuno-Allergology Laboratory of Clinical Chemistry and Pediatric Clinic, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0372-523X","authenticated-orcid":false,"given":"Ivan","family":"Taietti","sequence":"additional","affiliation":[{"name":"Pediatric Unit, Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, 27100 Pavia, Italy"},{"name":"Pediatric Clinic, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0029-9383","authenticated-orcid":false,"given":"Riccardo","family":"Castagnoli","sequence":"additional","affiliation":[{"name":"Pediatric Unit, Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, 27100 Pavia, Italy"},{"name":"Pediatric Clinic, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grazia","family":"Bossi","sequence":"additional","affiliation":[{"name":"Pediatric Clinic, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7084-5605","authenticated-orcid":false,"given":"Simone","family":"Foti Randazzese","sequence":"additional","affiliation":[{"name":"Pediatric Unit, Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, 27100 Pavia, Italy"},{"name":"Pediatric Clinic, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Marseglia","sequence":"additional","affiliation":[{"name":"Pediatric Clinic, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia Maria Elena","family":"Caimmi","sequence":"additional","affiliation":[{"name":"Pediatric Clinic, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1773-6482","authenticated-orcid":false,"given":"Amelia","family":"Licari","sequence":"additional","affiliation":[{"name":"Pediatric Unit, Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, 27100 Pavia, Italy"},{"name":"Pediatric Clinic, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1111\/j.1398-9995.2007.01347.x","article-title":"Anaphylaxis during anaesthesia: Diagnostic approach","volume":"62","author":"Ebo","year":"2007","journal-title":"Allergy"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.anai.2022.08.996","article-title":"Tryptase in type I hypersensitivity","volume":"130","author":"Michel","year":"2022","journal-title":"Ann. 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