{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T03:29:21Z","timestamp":1791689361382,"version":"4.3.4"},"reference-count":89,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2023,12,14]],"date-time":"2023-12-14T00:00:00Z","timestamp":1702512000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research Foundation Flanders\/Fonds Wetenschappelijk Onderzoek","award":["1800614N"],"award-info":[{"award-number":["1800614N"]}]},{"name":"Research Foundation Flanders\/Fonds Wetenschappelijk Onderzoek","award":["1804518N"],"award-info":[{"award-number":["1804518N"]}]},{"name":"Konsul T.H.C. Bergh Foundation, Sweden","award":["1800614N"],"award-info":[{"award-number":["1800614N"]}]},{"name":"Konsul T.H.C. Bergh Foundation, Sweden","award":["1804518N"],"award-info":[{"award-number":["1804518N"]}]},{"name":"Swedish Society of Medicine, Sweden","award":["1800614N"],"award-info":[{"award-number":["1800614N"]}]},{"name":"Swedish Society of Medicine, Sweden","award":["1804518N"],"award-info":[{"award-number":["1804518N"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Tryptase has proven to be a very useful and specific marker to demonstrate mast cell activation and degranulation when an acute (i.e., within 4 h after the event) and baseline value (i.e., at least 24 h after the event) are compared and meet the consensus formula (i.e., an increase of 20% + 2). The upper limit of normal determined by the manufacturer is 11.4 ng\/mL; however, this boundary has been the subject of debate. According to ECNM and AIM experts, the normal range of baseline tryptase should be 1 to 15 ng\/mL. A genetic trait, hereditary alpha tryptasemia, characterized by an increased alpha coding TPSAB1 copy number is associated with a baseline value above 8 ng\/mL. Elevated tryptase can also be found in chronic kidney disease, obesity, and hematological neoplasms. A tryptase &gt; 20 ng\/mL serves as a minor criterion to diagnose systemic mastocytosis and an increase in tryptase &gt; 20% + 2 during an acute event is a required criterion in the diagnosis of mast cell activation syndrome. The goal of this review is to demonstrate the (in)significance of tryptase using some clinical vignettes and to provide a practical guide on how to manage and interpret an elevated tryptase level.<\/jats:p>","DOI":"10.3390\/diagnostics13243662","type":"journal-article","created":{"date-parts":[[2023,12,14]],"date-time":"2023-12-14T03:58:02Z","timestamp":1702526282000},"page":"3662","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Diagnostic Significance of Tryptase for Suspected Mast Cell Disorders"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5571-9501","authenticated-orcid":false,"given":"Michiel","family":"Beyens","sequence":"first","affiliation":[{"name":"Faculty of Medicine and Health Sciences, Department of Immunology, Allergology and Rheumatology, Infla-Med Centre of Excellence, University of Antwerp, 2610 Antwerp, Belgium"},{"name":"Department of Immunology, Allergology and Rheumatology, University Hospital Antwerp, 2610 Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Toscano","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health Sciences, Department of Immunology, Allergology and Rheumatology, Infla-Med Centre of Excellence, University of Antwerp, 2610 Antwerp, Belgium"},{"name":"Department of Immunology, Allergology and Rheumatology, University Hospital Antwerp, 2610 Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Didier","family":"Ebo","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health Sciences, Department of Immunology, Allergology and Rheumatology, Infla-Med Centre of Excellence, University of Antwerp, 2610 Antwerp, Belgium"},{"name":"Department of Immunology, Allergology and Rheumatology, University Hospital Antwerp, 2610 Antwerp, Belgium"},{"name":"Department of Immunology and Allergology, AZ Jan Palfijn Gent, 9000 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1683-8882","authenticated-orcid":false,"given":"Theo","family":"G\u00fclen","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine and Allergy, K85, Karolinska University Hospital Huddinge, SE-14186 Stockholm, Sweden"},{"name":"Department of Medicine Solna, Division of Immunology and Allergy, Karolinska Institutet, SE-17177 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vito","family":"Sabato","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health Sciences, Department of Immunology, Allergology and Rheumatology, Infla-Med Centre of Excellence, University of Antwerp, 2610 Antwerp, Belgium"},{"name":"Department of Immunology, Allergology and Rheumatology, University Hospital Antwerp, 2610 Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1016\/j.jaci.2004.02.032","article-title":"Expression of alpha-tryptase and beta-tryptase by human basophils","volume":"113","author":"Min","year":"2004","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.molimm.2014.04.001","article-title":"Human mast cell tryptase in biology and medicine","volume":"63","author":"Vitte","year":"2015","journal-title":"Mol. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"11939","DOI":"10.1016\/S0021-9258(19)68496-6","article-title":"Tryptase from human pulmonary mast cells. Purification and characterization","volume":"256","author":"Schwartz","year":"1981","journal-title":"J. Biol. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3355","DOI":"10.1074\/jbc.274.6.3355","article-title":"Characterization of genes encoding known and novel human mast cell tryptases on chromosome 16p13.3","volume":"274","author":"Pallaoro","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1016\/j.jaci.2006.02.026","article-title":"Tryptase genetics and anaphylaxis","volume":"117","author":"Caughey","year":"2006","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"49169","DOI":"10.1074\/jbc.M108677200","article-title":"Human tryptase epsilon (PRSS22), a new member of the chromosome 16p13.3 family of human serine proteases expressed in airway epithelial cells","volume":"276","author":"Wong","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Sprinzl, B., Greiner, G., Uyanik, G., Arock, M., Haferlach, T., Sperr, W.R., Valent, P., and Hoermann, G. (2021). Genetic Regulation of Tryptase Production and Clinical Impact: Hereditary Alpha Tryptasemia, Mastocytosis and Beyond. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22052458"},{"key":"ref_8","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_9","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1007\/BF01533368","article-title":"Development of a new, more sensitive immunoassay for human tryptase: Use in systemic anaphylaxis","volume":"14","author":"Schwartz","year":"1994","journal-title":"J. Clin. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1159\/000501079","article-title":"Why the 20% + 2 Tryptase Formula Is a Diagnostic Gold Standard for Severe Systemic Mast Cell Activation and Mast Cell Activation Syndrome","volume":"180","author":"Valent","year":"2019","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3051","DOI":"10.1016\/j.jaip.2021.03.050","article-title":"Mast Cell Activation During Suspected Perioperative Hypersensitivity: A Need for Paired Samples Analysis","volume":"9","author":"Ebo","year":"2021","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1941","DOI":"10.1016\/j.jaip.2022.05.007","article-title":"Global Classification of Mast Cell Activation Disorders: An ICD-10-CM-Adjusted Proposal of the ECNM-AIM Consortium","volume":"10","author":"Valent","year":"2022","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1159\/000524532","article-title":"Mast Cell Activation Syndromes: Collegium Internationale Allergologicum Update 2022","volume":"183","author":"Valent","year":"2022","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1002\/ajh.26962","article-title":"Systemic mastocytosis in adults: 2023 update on diagnosis, risk stratification and management","volume":"98","author":"Pardanani","year":"2023","journal-title":"Am. J. Hematol."},{"key":"ref_15","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_16","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1038\/ng.3696","article-title":"Elevated basal serum tryptase identifies a multisystem disorder associated with increased TPSAB1 copy number","volume":"48","author":"Lyons","year":"2016","journal-title":"Nat. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1016\/j.jaci.2021.06.017","article-title":"Hereditary alpha tryptasemia is not associated with specific clinical phenotypes","volume":"149","author":"Chollet","year":"2022","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3549","DOI":"10.1016\/j.jaip.2020.05.057","article-title":"Hereditary Alpha-Tryptasemia: UK Prevalence and Variability in Disease Expression","volume":"8","author":"Robey","year":"2020","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1080\/17843286.2022.2137631","article-title":"Mastocytosis and related entities: A practical roadmap","volume":"78","author":"Beyens","year":"2022","journal-title":"Acta Clin. Belg."},{"key":"ref_20","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_21","doi-asserted-by":"crossref","first-page":"1998","DOI":"10.1016\/j.jaip.2023.05.015","article-title":"Extrinsic and Intrinsic Modulators of Anaphylaxis","volume":"11","author":"Carter","year":"2023","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_22","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_23","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1016\/j.jaci.2021.08.007","article-title":"Defining baseline variability of serum tryptase levels improves accuracy in identifying anaphylaxis","volume":"149","author":"Mateja","year":"2022","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.iac.2006.05.010","article-title":"Diagnostic value of tryptase in anaphylaxis and mastocytosis","volume":"26","author":"Schwartz","year":"2006","journal-title":"Immunol. Allergy Clin. N. Am."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1111\/all.14663","article-title":"Mediators of anaphylactic reactions: Tryptase and histamine stability in whole blood","volume":"76","author":"Serrier","year":"2021","journal-title":"Allergy"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.reval.2022.02.218","article-title":"Tryptase and anaphylaxis: The case for systematic paired samples in all settings, from the playground to the COVID-19 vaccination center","volume":"62","author":"Vitte","year":"2022","journal-title":"Rev. Fr. Allergol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1111\/j.1365-2222.2011.03848.x","article-title":"An increase in serum tryptase even below 11.4 ng\/mL may indicate a mast cell-mediated hypersensitivity reaction: A prospective study in Hymenoptera venom allergic patients","volume":"41","author":"Haeberli","year":"2011","journal-title":"Clin. Exp. Allergy"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1111\/cea.12785","article-title":"A 17-year experience in perioperative anaphylaxis 1998-2015: Harmonizing optimal detection of mast cell mediator release","volume":"46","author":"Egner","year":"2016","journal-title":"Clin Exp Allergy"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1159\/000339749","article-title":"Usefulness and limitations of sequential serum tryptase for the diagnosis of anaphylaxis in 102 patients","volume":"160","author":"Cardona","year":"2013","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_30","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_31","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1056\/NEJM199208063270603","article-title":"Fatal and near-fatal anaphylactic reactions to food in children and adolescents","volume":"327","author":"Sampson","year":"1992","journal-title":"N. Engl. J. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1159\/000518319","article-title":"Characteristics and Laboratory Findings of Food-Induced Anaphylaxis in Children: Study in an Asian Developing Country","volume":"183","author":"Nantanee","year":"2022","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1692","DOI":"10.1016\/j.jaip.2018.01.006","article-title":"Diagnostic Value of Tryptase in Food Allergic Reactions: A Prospective Study of 160 Adult Peanut Challenges","volume":"6","author":"Dua","year":"2018","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1016\/j.jaci.2022.04.025","article-title":"Differential mast cell mediators in systemic mastocytosis and hereditary \u03b1-tryptasemia","volume":"150","author":"Giannetti","year":"2022","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.1016\/j.jaip.2022.03.008","article-title":"Nontryptase Urinary and Hematologic Biomarkers of Mast Cell Expansion and Mast Cell Activation: Status 2022","volume":"10","author":"Butterfield","year":"2022","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"419","DOI":"10.18176\/jiaci.0854","article-title":"Anaphylaxis: Mediators, Biomarkers, and Microenvironments","volume":"32","author":"Esteban","year":"2022","journal-title":"J. Investig. Allergol. Clin. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1007\/s40521-022-00326-1","article-title":"New Biomarkers in Anaphylaxis (Beyond Tryptase)","volume":"9","year":"2022","journal-title":"Curr. Treat. Options Allergy"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1111\/cea.14110","article-title":"Tryptase release does not discriminate between IgE- and MRGPRX2-mediated activation in human mast cells","volume":"52","author":"Elst","year":"2022","journal-title":"Clin. Exp. Allergy"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1007\/s10875-019-00707-3","article-title":"Serum Tryptase Cannot Differentiate Vancomycin-Induced Anaphylaxis From Red Man Syndrome","volume":"39","author":"Noguchi","year":"2019","journal-title":"J. Clin. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1007\/s10875-018-0506-y","article-title":"First Identification of an Inherited TPSAB1 Quintuplication in a Patient with Clonal Mast Cell Disease","volume":"38","author":"Sabato","year":"2018","journal-title":"J. Clin. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3003","DOI":"10.1111\/all.15790","article-title":"Basal serum tryptase: A critical reconsideration of reference values","volume":"78","author":"Francois","year":"2023","journal-title":"Allergy"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2348","DOI":"10.1084\/jem.20190701","article-title":"Impact of naturally forming human \u03b1\/\u03b2-tryptase heterotetramers in the pathogenesis of hereditary \u03b1-tryptasemia","volume":"216","author":"Le","year":"2019","journal-title":"J. Exp. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3010","DOI":"10.1016\/j.jaip.2023.08.008","article-title":"The Normal Range of Baseline Tryptase Should Be 1 to 15 ng\/mL and Covers Healthy Individuals With H\u03b1T","volume":"11","author":"Valent","year":"2023","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1796","DOI":"10.1182\/bloodadvances.2022007936","article-title":"Genetically defined individual reference ranges for tryptase limit unnecessary procedures and unmask myeloid neoplasms","volume":"7","author":"Chovanec","year":"2023","journal-title":"Blood Adv."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1016\/j.jaci.2013.11.039","article-title":"Mendelian inheritance of elevated serum tryptase associated with atopy and connective tissue abnormalities","volume":"133","author":"Lyons","year":"2014","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1016\/j.jaci.2014.06.007","article-title":"Familial hypertryptasemia with associated mast cell activation syndrome","volume":"134","author":"Sabato","year":"2014","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1016\/j.jaci.2020.11.017","article-title":"Patients with mast cell activation symptoms and elevated baseline serum tryptase level have unique bone marrow morphology","volume":"147","author":"Giannetti","year":"2021","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/j.jaci.2020.06.035","article-title":"Heritable risk for severe anaphylaxis associated with increased \u03b1-tryptase-encoding germline copy number at TPSAB1","volume":"147","author":"Lyons","year":"2021","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/j.anai.2021.08.009","article-title":"Clinical relevance of inherited genetic differences in human tryptases: Hereditary alpha-tryptasemia and beyond","volume":"127","author":"Glover","year":"2021","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.iac.2021.09.007","article-title":"Anaphylaxis and Mast Cell Disorders","volume":"42","author":"Akin","year":"2022","journal-title":"Immunol. Allergy Clin. N. Am."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1182\/blood.2020006157","article-title":"Hereditary \u03b1 tryptasemia is a valid genetic biomarker for severe mediator-related symptoms in mastocytosis","volume":"137","author":"Greiner","year":"2021","journal-title":"Blood"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1016\/j.jaip.2022.03.007","article-title":"Personalized Management Strategies in Mast Cell Disorders: ECNM-AIM User\u2019s Guide for Daily Clinical Practice","volume":"10","author":"Valent","year":"2022","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1016\/j.jaci.2023.07.014","article-title":"Severe food allergy reactions are associated with \u03b1-tryptase","volume":"152","author":"Lang","year":"2023","journal-title":"J Allergy Clin. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Gonz\u00e1lez-de-Olano, D., Navarro-Navarro, P., Mu\u00f1oz-Gonz\u00e1lez, J.I., S\u00e1nchez-Mu\u00f1oz, L., Henriques, A., de-Andr\u00e9s-Mart\u00edn, A., Peralta-Arjonilla, D., Mayado, A., Jara-Acevedo, M., and Garc\u00eda-Montero, A.C. (Allergy, 2023). Clinical impact of the TPSAB1 genotype in mast cell diseases: A REMA study in a cohort of 959 individuals, Allergy, epub ahead of print.","DOI":"10.1111\/all.15911"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"152","DOI":"10.23822\/EurAnnACI.1764-1489.288","article-title":"Defining hereditary alpha-tryptasemia as a risk\/modifying factor for anaphylaxis: Are we there yet?","volume":"55","author":"Couto","year":"2023","journal-title":"Eur. Ann. Allergy Clin. Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e646","DOI":"10.1097\/HS9.0000000000000646","article-title":"Updated Diagnostic Criteria and Classification of Mast Cell Disorders: A Consensus Proposal","volume":"5","author":"Valent","year":"2021","journal-title":"Hemasphere"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1159\/000329856","article-title":"Validation of the REMA score for predicting mast cell clonality and systemic mastocytosis in patients with systemic mast cell activation symptoms","volume":"157","author":"Matito","year":"2012","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.jaci.2017.05.036","article-title":"A distinct biomolecular profile identifies monoclonal mast cell disorders in patients with idiopathic anaphylaxis","volume":"141","author":"Carter","year":"2018","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1111\/cea.12369","article-title":"The presence of mast cell clonality in patients with unexplained anaphylaxis","volume":"44","author":"Sander","year":"2014","journal-title":"Clin. Exp. Allergy"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1016\/j.jaip.2023.05.012","article-title":"Disease Spectrum of Anaphylaxis Disorders","volume":"11","author":"Cain","year":"2023","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1016\/j.jaip.2017.02.008","article-title":"Risk Factor Analysis of Anaphylactic Reactions in Patients With Systemic Mastocytosis","volume":"5","author":"Ljung","year":"2017","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1016\/j.jaci.2019.07.037","article-title":"Detection of KIT D816V mutation in patients with severe anaphylaxis and normal basal tryptase-first data from the Anaphylaxis Registry (NORA)","volume":"144","author":"Siebenhaar","year":"2019","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.jaci.2012.12.1578","article-title":"Higher mast cell load decreases the risk of Hymenoptera venom-induced anaphylaxis in patients with mastocytosis","volume":"132","year":"2013","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/j.jaci.2021.02.043","article-title":"Routine KIT p.D816V screening identifies clonal mast cell disease in patients with Hymenoptera allergy regularly missed using baseline tryptase levels alone","volume":"148","author":"Rijavec","year":"2021","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.jaci.2014.11.035","article-title":"Clonal mast cell disorders in patients with severe Hymenoptera venom allergy and normal serum tryptase levels","volume":"136","author":"Zanotti","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.6004\/jnccn.2018.0088","article-title":"Systemic Mastocytosis, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology","volume":"16","author":"Gotlib","year":"2018","journal-title":"J. Natl. Compr. Cancer Netw."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1373\/clinchem.2017.277897","article-title":"Digital PCR: A Sensitive and Precise Method for KIT D816V Quantification in Mastocytosis","volume":"64","author":"Greiner","year":"2018","journal-title":"Clin. Chem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"3176","DOI":"10.1016\/j.jaip.2021.04.062","article-title":"Diagnosis of Primary Mast Cell Disorders in Anaphylaxis: Value of KIT D816V in Peripheral Blood","volume":"9","author":"Ebo","year":"2021","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e12174","DOI":"10.1002\/clt2.12174","article-title":"Detection of clonal mast cell disease in wasp venom allergic patients with normal tryptase","volume":"12","author":"Onnes","year":"2022","journal-title":"Clin. Transl. Allergy"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1111\/joim.12410","article-title":"Mastocytosis: The puzzling clinical spectrum and challenging diagnostic aspects of an enigmatic disease","volume":"279","author":"Nilsson","year":"2016","journal-title":"J. Intern. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2015","DOI":"10.1016\/j.jaip.2022.05.037","article-title":"Refined Treatment Response Criteria for Indolent Systemic Mastocytosis Proposed by the ECNM-AIM Consortium","volume":"10","author":"Pyatilova","year":"2022","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1159\/000059404","article-title":"Serum tryptase levels in patients with mastocytosis: Correlation with mast cell burden and implication for defining the category of disease","volume":"128","author":"Sperr","year":"2002","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_73","first-page":"282","article-title":"Serum tryptase levels and markers of renal dysfunction in a population with chronic kidney disease","volume":"23","author":"Sirvent","year":"2010","journal-title":"J. Nephrol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1159\/000260080","article-title":"Tryptase is not cleared by the kidneys into the urine","volume":"152","author":"Simon","year":"2010","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2681","DOI":"10.1084\/jem.183.6.2681","article-title":"Recombinant human stem cell factor (kit ligand) promotes human mast cell and melanocyte hyperplasia and functional activation in vivo","volume":"183","author":"Costa","year":"1996","journal-title":"J. Exp. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2833","DOI":"10.1111\/all.15369","article-title":"Tryptase reference ranges are age-dependent in a large population-based cohort","volume":"77","author":"Slot","year":"2022","journal-title":"Allergy"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1016\/j.jaci.2014.05.047","article-title":"Diminished reliability of tryptase as risk indicator of mastocytosis in older overweight subjects","volume":"135","author":"Vos","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_78","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_79","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1111\/j.1398-9995.2008.01731.x","article-title":"Elevated levels of tryptase in children with nummular eczema","volume":"63","author":"Lange","year":"2008","journal-title":"Allergy"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1111\/acer.12682","article-title":"Serum concentrations of mast cell tryptase are reduced in heavy drinkers","volume":"39","author":"Beceiro","year":"2015","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.taap.2004.09.003","article-title":"Exposure to tobacco-derived materials induces overproduction of secreted proteinases in mast cells","volume":"204","author":"Turner","year":"2005","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/j.jaip.2017.08.039","article-title":"Persistent tryptase elevation in a patient with Gaucher disease","volume":"6","author":"Schussler","year":"2018","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1016\/j.jaci.2005.07.023","article-title":"False-elevated serum tryptase assay result caused by heterophilic antibodies","volume":"116","author":"Boonstra","year":"2005","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"3918","DOI":"10.1016\/j.jaip.2021.06.011","article-title":"Selecting the Right Criteria and Proper Classification to Diagnose Mast Cell Activation Syndromes: A Critical Review","volume":"9","author":"Akin","year":"2021","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1016\/j.jaip.2018.11.045","article-title":"Doctor, I Think I Am Suffering from MCAS: Differential Diagnosis and Separating Facts from Fiction","volume":"7","author":"Valent","year":"2019","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/j.iac.2023.04.010","article-title":"Management of Mediator Symptoms, Allergy, and Anaphylaxis in Mastocytosis","volume":"43","author":"Gulen","year":"2023","journal-title":"Immunol. Allergy Clin. N. Am."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2542","DOI":"10.1016\/j.jaip.2023.02.017","article-title":"Increased Excretion of Mast Cell Mediator Metabolites During Mast Cell Activation Syndrome","volume":"11","author":"Butterfield","year":"2023","journal-title":"J. Allergy Clin. Immunol. 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Allergy Immunol."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/13\/24\/3662\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:38:33Z","timestamp":1760132313000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/13\/24\/3662"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,14]]},"references-count":89,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["diagnostics13243662"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics13243662","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,14]]}}}