{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T19:33:00Z","timestamp":1790019180224,"version":"4.0.1"},"reference-count":45,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,8,23]],"date-time":"2024-08-23T00:00:00Z","timestamp":1724371200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Introduction: Tryptase is an important biomarker widely used in the laboratory confirmation of severe hypersensitivity reactions, especially anaphylaxis. It also plays a crucial role in the diagnosis, risk stratification, management and prognostic evaluation of many other mast cell-related conditions. Aim: This paper aims to highlight the role of serum tryptase, both in allergic disorders and other mast cell-related conditions. Two clinical cases regarding timely serum tryptase acquisition (in drug hypersensitivity reactions during the imaging procedure and perioperative anaphylaxis) are meant to emphasize the clinical potential of this protease. Method: We performed a comprehensive literature search of the PubMed\/Medline and Scopus databases. From a total of 640 subject related publications, dating from 1940 to 2024, 45 articles written in English were selected. Literature search results: Total serum tryptase is a simple, cost-effective analysis with a normal baseline tryptase (sBT) level below 8.4 \u00b5g\/L. Elevated sBT can indicate hereditary alpha-tryptasemia (H\u03b1T), mastocytosis and other non-allergic disorders. Patients with higher sBT levels, especially with insect venom allergy, have an increased risk of severe reactions and thereby require a prolonged treatment. All immediate systemic hypersensitivity reactions require a correlation between serum acute tryptase (sAT) and sBT. According to the guidelines, measuring sAT 30 min to 2 h after the symptom onset and sBT 24 h after the resolution, using the 20 + 2 rule and an sAT\/sBT ratio of 1.685, improves the diagnostic accuracy in anaphylaxis. Conclusions: Tryptase levels should be acquired in all cases with clinical suspicion of MC degranulation. Given the increasing clinical relevance, elevated baseline serum tryptase levels require a multidisciplinary approach and further investigation.<\/jats:p>","DOI":"10.3390\/medicina60091380","type":"journal-article","created":{"date-parts":[[2024,8,23]],"date-time":"2024-08-23T12:38:43Z","timestamp":1724416723000},"page":"1380","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Tryptase: The Silent Witness of Past and Ongoing Systemic Events"],"prefix":"10.3390","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0944-9675","authenticated-orcid":false,"given":"Irena","family":"O\u0161tri\u0107 Pavlovi\u0107","sequence":"first","affiliation":[{"name":"Clinic of Allergology and Immunology, University Clinical Centre of Serbia, 11000 Belgrade, Serbia"},{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Radovi\u0107","sequence":"additional","affiliation":[{"name":"Clinic of Allergology and Immunology, University Clinical Centre of Serbia, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3989-0113","authenticated-orcid":false,"given":"Danka","family":"Krtini\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jelena","family":"Spiri\u0107","sequence":"additional","affiliation":[{"name":"Clinic of Gastroenterology and Hepatology, University Clinical Centre of Serbia, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9727-7128","authenticated-orcid":false,"given":"Nata\u0161a","family":"Kusi\u0107","sequence":"additional","affiliation":[{"name":"Clinic of Allergology and Immunology, University Clinical Centre of Serbia, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonije","family":"Veli\u010dkovi\u0107","sequence":"additional","affiliation":[{"name":"Clinic of Allergology and Immunology, University Clinical Centre of Serbia, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7047-3538","authenticated-orcid":false,"given":"Vesna","family":"Tomi\u0107-Spiri\u0107","sequence":"additional","affiliation":[{"name":"Clinic of Allergology and Immunology, University Clinical Centre of Serbia, 11000 Belgrade, Serbia"},{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Gilfillan, A.M., Austin, S.J., and Metcalfe, D.D. (2011). Mast Cell Biology: Introduction and Overview. Mast Cell Biology, Springer.","DOI":"10.1007\/978-1-4419-9533-9"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Krystel-Whittemore, M., Dileepan, K.N., and Wood, J.G. (2016). Mast Cell: A Multi-Functional Master Cell. Front. Immunol., 6.","DOI":"10.3389\/fimmu.2015.00620"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1111\/j.1365-2044.2004.03757.x","article-title":"Mast cell tryptase: A review of its physiology and clinical significance","volume":"59","author":"Kayne","year":"2004","journal-title":"Anaesthesia"},{"key":"ref_4","unstructured":"Phadia, A.B. (2024, April 15). ImmunoCAP(TM) Tryptase. Available online: https:\/\/dfu.phadia.com\/Data\/Pdf\/5bfd303689c2320848d8449f.pdf."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/anae.12926","article-title":"Laboratory investigation of anaphylaxis: Not as easy as it seems","volume":"70","author":"Sheldon","year":"2015","journal-title":"Anaesthesia"},{"key":"ref_6","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":"2023","journal-title":"Ann. Allergy Asthma Immunol. Off. Publ. Am. Coll. Allergy Asthma Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2994","DOI":"10.1016\/j.jaip.2021.03.011","article-title":"Use and Interpretation of Acute and Baseline Tryptase in Perioperative Hypersensitivity and Anaphylaxis","volume":"9","author":"Vitte","year":"2021","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2424","DOI":"10.1016\/j.jaip.2021.12.031","article-title":"Elevated Basal Serum Tryptase: Disease Distribution and Variability in a Regional Health System","volume":"10","author":"Waters","year":"2022","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/j.anai.2021.06.019","article-title":"Inherited and acquired determinants of serum tryptase levels in humans","volume":"127","author":"Lyons","year":"2021","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.iac.2018.04.003","article-title":"Hereditary alpha tryptasemia: Genotyping and associated clinical features","volume":"38","author":"Lyons","year":"2018","journal-title":"Immunol. Allergy Clin. N. Am."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1111\/cea.14264","article-title":"Clonal mast cell disorders and hereditary \u03b1-tryptasemia as risk factors for anaphylaxis","volume":"53","author":"Rijavec","year":"2023","journal-title":"Clin. Exp. Allergy"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.jaip.2014.03.007","article-title":"Mast Cell Activation Disorders","volume":"2","author":"Akin","year":"2014","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_13","first-page":"2348","article-title":"Mast cell activation syndromes\u2014Evaluation of current diagnostic criteria and laboratory tools in clinical practice (Review)","volume":"20","author":"Leru","year":"2020","journal-title":"Exp. Ther. Med."},{"key":"ref_14","unstructured":"Burks, A.W., O\u2019Hehir, R.E., Broide, D.H., Holgate, S.T., Bacharier, L.B., Hershey, G.K.K., and Peebles, R.S. (2019). Middleton\u2019s Allergy: Principles and Practice, Elsevier Health Sciences."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1586\/17474086.2014.955008","article-title":"The serum tryptase test: An emerging robust biomarker in clinical hematology","volume":"7","author":"Valent","year":"2014","journal-title":"Expert Rev. Hematol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"S44","DOI":"10.1016\/j.pathol.2016.12.105","article-title":"Tryptase and renal failure: A retrospective audit of routine laboratory samples","volume":"49","author":"Pucar","year":"2017","journal-title":"Pathology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1111\/eci.12622","article-title":"Serum tryptase concentration and progression to end-stage renal disease","volume":"46","author":"Jesky","year":"2016","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1161\/ATVBAHA.114.303570","article-title":"Mast Cells as Effectors in Atherosclerosis","volume":"35","author":"Bot","year":"2015","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"395173","DOI":"10.1155\/2015\/395173","article-title":"Elevated Serum Tryptase and Endothelin in Patients with ST Segment Elevation Myocardial Infarction: Preliminary Report","volume":"2015","author":"Lewicki","year":"2015","journal-title":"Mediat. Inflamm."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1002\/clc.4950260804","article-title":"Tryptase levels in patients after acute coronary syndromes: The potential new marker of an unstable plaque?","volume":"26","author":"Filipiak","year":"2003","journal-title":"Clin. Cardiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e000472","DOI":"10.1136\/openhrt-2016-000472","article-title":"Mast cells and acute coronary syndromes: Relationship between serum tryptase, clinical outcome and severity of coronary artery disease","volume":"3","author":"Morici","year":"2016","journal-title":"Open Hear."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"S498","DOI":"10.14309\/00000434-200910003-01333","article-title":"Evaluation on the Diagnostic Utility of Serum Tryptase Level in Irritable Bowel Syndrome: 1333","volume":"104","author":"Wang","year":"2009","journal-title":"Off. J. Am. Coll. Gastroenterol. ACG"},{"key":"ref_23","first-page":"22","article-title":"Irritable bowel syndrome and basal serum tryptase: The correlation between subtype, severity and comorbidities. a pilot study","volume":"114","author":"Pastor","year":"2022","journal-title":"Rev. Esp. Enfermadades Dig."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"S38","DOI":"10.14309\/00000434-201210001-00088","article-title":"Tryptase: A New Measure (or Predictor) of the Extent of GI Involvement in Eosinophilic Esophagitis (EoE)?: 88","volume":"107","author":"Bridge","year":"2012","journal-title":"Off. J. Am. Coll. Gastroenterol. ACG"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1093\/ibd\/izaa125","article-title":"Mast Cell Tryptase Promotes Inflammatory Bowel Disease\u2013Induced Intestinal Fibrosis","volume":"27","author":"Liu","year":"2021","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.21037\/tcr.2017.08.43","article-title":"Changes of tryptase in patients with hepatocellular carcinoma after transarterial chemoembolization","volume":"6","author":"Min","year":"2017","journal-title":"Transl. Cancer Res."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Lu, F., and Huang, S. (2017). The Roles of Mast Cells in Parasitic Protozoan Infections. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.00363"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1086\/344318","article-title":"Association of Transient Dermal Mastocytosis and Elevated Plasma Tryptase Levels with Development of Adverse Reactions after Treatment of Onchocerciasis with Ivermectin","volume":"186","author":"Cooper","year":"2002","journal-title":"J. Infect. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1111\/all.12350","article-title":"International Consensus on drug allergy","volume":"69","author":"Demoly","year":"2014","journal-title":"Allergy"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1007\/s12024-018-9980-z","article-title":"Diagnostic role of serum tryptase in anaphylactic deaths in forensic medicine: A systematic review and meta-analysis","volume":"14","author":"Sun","year":"2018","journal-title":"Forensic Sci. Med. Pathol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1007\/s12024-021-00373-1","article-title":"Postmortem diagnostics of assumed suicidal food anaphylaxis in prison: A unique case of anaphylactic death due to peach ingestion","volume":"17","author":"Tambuzzi","year":"2021","journal-title":"Forensic Sci. Med. Pathol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"100472","DOI":"10.1016\/j.waojou.2020.100472","article-title":"World Allergy Organization Anaphylaxis Guidance 2020","volume":"13","author":"Cardona","year":"2020","journal-title":"World Allergy Organ. J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1111\/all.15032","article-title":"EAACI guidelines: Anaphylaxis (2021 update)","volume":"77","author":"Muraro","year":"2022","journal-title":"Allergy"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1111\/all.13752","article-title":"Paired acute-baseline serum tryptase levels in perioperative anaphylaxis: An observational study","volume":"74","author":"Vitte","year":"2019","journal-title":"Allergy"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1159\/000328760","article-title":"Definitions, criteria and global classification of mast cell disorders with special reference to mast cell activation syndromes: A consensus proposal","volume":"157","author":"Valent","year":"2012","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2031","DOI":"10.1111\/all.13226","article-title":"Validation of international consensus equation for acute serum total tryptase in mast cell activation: A perioperative perspective","volume":"72","author":"Baretto","year":"2017","journal-title":"Allergy"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1016\/j.jaip.2017.06.021","article-title":"Anaphylaxis and Clinical Utility of Real-World Measurement of Acute Serum Tryptase in UK Emergency Departments","volume":"5","author":"Buka","year":"2017","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1097\/00130832-200208000-00008","article-title":"Epidemiology of hymenoptera allergy","volume":"2","author":"Antonicelli","year":"2002","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1016\/j.jaip.2019.11.027","article-title":"Global Trends in Anaphylaxis Epidemiology and Clinical Implications","volume":"8","author":"Turner","year":"2020","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1111\/all.13262","article-title":"EAACI guidelines on allergen immunotherapy: Hymenoptera venom allergy","volume":"73","author":"Sturm","year":"2017","journal-title":"Allergy"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Blank, S., Grosch, J., Ollert, M., and Bil\u00f2, M.B. (2020). Precision Medicine in Hymenoptera Venom Allergy: Diagnostics, Biomarkers, and Therapy of Different Endotypes and Phenotypes. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.579409"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"162","DOI":"10.18176\/jiaci.0363","article-title":"Basal Tryptase Levels Can Predict Clinical Severity in Hymenoptera Venom Anaphylaxis and Ischemic Cardiovascular Disorders","volume":"29","author":"Farioli","year":"2019","journal-title":"J. Investig. Allergol. Clin. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1097\/ACI.0000000000000569","article-title":"Tryptase values in anaphylaxis and insect allergy","volume":"19","author":"Bonadonna","year":"2019","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1159\/000506199","article-title":"Elevated Serum Tryptase in Non-Anaphylaxis Cases: A Concise Review","volume":"181","author":"Lee","year":"2020","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"100595","DOI":"10.1016\/j.ijso.2023.100595","article-title":"Management of perioperative anaphylaxis: Systematic review","volume":"52","author":"Admass","year":"2023","journal-title":"Int. J. Surg. Open"}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/60\/9\/1380\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:42:05Z","timestamp":1760110925000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/60\/9\/1380"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,23]]},"references-count":45,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["medicina60091380"],"URL":"https:\/\/doi.org\/10.3390\/medicina60091380","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,23]]}}}