Reversible Elevation of Tryptase Over the Individual's Baseline: Why is It the Best Biomarker for Severe Systemic Mast Cell Activation and MCAS?

Metcalfe DD. Mast cells and mastocytosis. Blood. 2008;112:946–56.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Galli SJ, Tsai M. IgE and mast cells in allergic disease. Nat Med. 2012;18:693–704.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Theoharides TC, Valent P, Akin C. Mast cells, mastocytosis, and related disorders. N Engl J Med. 2015;373:163–72.

Article  CAS  PubMed  Google Scholar 

• Valent P, Akin C, Hartmann K, Nilsson G, Reiter A, Hermine O, et al. Mast cells as a unique hematopoietic lineage and cell system: From Paul Ehrlich’s visions to precision medicine concepts. Theranostics. 2020;10:10743–68. This article describes that the mast cell system forms a unique hematopoietic cell lineage with unique features and unique functional properties in health and disease.

Article  CAS  PubMed  PubMed Central  Google Scholar 

• Valent P, Akin C, Sperr WR, Horny HP, Arock M, Metcalfe DD, Galli SJ. New insights into the pathogenesis of mastocytosis: emerging concepts in diagnosis and therapy. Annu Rev Pathol. 2023;18:361–86. Comprehensive review on the pathogenesis and pathology of mast cells in patients with mast cell proliferative disorders (mastocytosis) and mast cell activation disorders.

Article  CAS  PubMed  Google Scholar 

Metcalfe DD, Peavy RD, Gilfillan AM. Mechanisms of mast cell signaling in anaphylaxis. J Allergy Clin Immunol. 2009;124:639–46.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kalesnikoff J, Galli SJ. Anaphylaxis: mechanisms of mast cell activation. Chem Immunol Allergy. 2010;95:45–66.

Article  CAS  PubMed  Google Scholar 

Lieberman P. Mechanisms of anaphylaxis beyond classically mediated antigen- and IgE-induced events. Ann Allergy Asthma Immunol. 2017;118:246–8.

Article  PubMed  Google Scholar 

Galli SJ, Gaudenzio N, Tsai M. Mast cells in inflammation and disease: recent progress and ongoing concerns. Annu Rev Immunol. 2020;38:49–77.

Article  CAS  PubMed  Google Scholar 

Schwartz LB. Tryptase from human mast cells: biochemistry, biology and clinical utility. Monogr Allergy. 1990;27:90–113.

CAS  PubMed  Google Scholar 

Schwartz LB. Tryptase, a mediator of human mast cells. J Allergy Clin Immunol. 1990;86:594–8.

Article  CAS  PubMed  Google Scholar 

• Schwartz LB, Lewis RA, Austen KF. Tryptase from human pulmonary mast cells. Purification and characterization J Biol Chem. 1981;256:11939–43. Isolation and biochemical characterization of human tryptase from tissue mast cells.

CAS  PubMed  Google Scholar 

Jogie-Brahim S, Min HK, Fukuoka Y, Xia HZ, Schwartz LB. Expression of alpha-tryptase and beta-tryptase by human basophils. J Allergy Clin Immunol. 2004;113:1086–92.

Article  CAS  PubMed  Google Scholar 

Schwartz LB, Min HK, Ren S, Xia HZ, Hu J, Zhao W, et al. Tryptase precursors are preferentially and spontaneously released, whereas mature tryptase is retained by HMC-1 cells, Mono-Mac-6 cells, and human skin-derived mast cells. J Immunol. 2003;170:5667–73.

Article  CAS  PubMed  Google Scholar 

Fukuoka Y, Schwartz LB. The B12 anti-tryptase monoclonal antibody disrupts the tetrameric structure of heparin-stabilized beta-tryptase to form monomers that are inactive at neutral pH and active at acidic pH. J Immunol. 2006;176:3165–72.

Article  CAS  PubMed  Google Scholar 

Skarbø BR, Vinnes EW, Wentzel-Larsen T, Sylte MS, Apelseth TO. Estimating the within-subject (CVI) and between-subject (CVG) biological variation of serum tryptase. Immun Inflamm Dis. 2022;10: e578.

Article  PubMed  Google Scholar 

Chovanec J, Tunc I, Hughes J, Halstead J, Mateja A, Liu Y, et al. Genetically defined individual reference ranges for tryptase limit unnecessary procedures and unmask myeloid neoplasms. Blood Adv. 2023;7:1796–810.

Article  CAS  PubMed  Google Scholar 

• Valent P, Hoermann G, Bonadonna P, Hartmann K, Sperr WR, Broesby-Olsen S, et al. The normal range of baseline tryptase should be 1 to 15 ng/mL and covers healthy individuals with HαT. J Allergy Clin Immunol Pract. 2023;11:3010–20. Description of biological ranges of basal serum tryptase in healthy subjects, including cohorts with or without carriers of hereditary alpha tryptasemia.

Article  CAS  PubMed  Google Scholar 

Sperr WR, Jordan JH, Fiegl M, Escribano L, Bellas C, Dirnhofer S, et al. Serum tryptase levels in patients with mastocytosis: correlation with mast cell burden and implication for defining the category of disease. Int Arch Allergy Immunol. 2002;128:136–41.

Article  CAS  PubMed  Google Scholar 

Sperr WR, Stehberger B, Wimazal F, Baghestanian M, Schwartz LB, Kundi M, et al. Serum tryptase measurements in patients with myelodysplastic syndromes. Leuk Lymphoma. 2002;43:1097–105.

Article  CAS  PubMed  Google Scholar 

Sperr WR, El-Samahi A, Kundi M, Girschikofsky M, Winkler S, Lutz D, et al. Elevated tryptase levels selectively cluster in myeloid neoplasms: a novel diagnostic approach and screen marker in clinical hematology. Eur J Clin Invest. 2009;39:914–23.

Article  CAS  PubMed  Google Scholar 

Valent P, Sperr WR, Sotlar K, Reiter A, Akin C, Gotlib J, et al. The serum tryptase test: an emerging robust biomarker in clinical hematology. Expert Rev Hematol. 2014;7:683–90.

Article  CAS  PubMed  PubMed Central  Google Scholar 

•• Schwartz LB, Metcalfe DD, Miller JS, Earl H, Sullivan T. Tryptase levels as an indicator of mast-cell activation in systemic anaphylaxis and mastocytosis. N Engl J Med. 1987;316:1622–6. First description that an event-related elevation of serum tryptase over the individual´s baseline is a robust biochemical marker of anaphylaxis.

Article  CAS  PubMed  Google Scholar 

Schwartz LB, Sakai K, Bradford TR, Ren S, Zweiman B, Worobec AS, Metcalfe DD. The alpha form of human tryptase is the predominant type present in blood at baseline in normal subjects and is elevated in those with systemic mastocytosis. J Clin Invest. 1995;96:2702–10.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Schwartz HJ. Elevated serum tryptase in exercise-induced anaphylaxis. J Allergy Clin Immunol. 1995;95:917–9.

Article  CAS  PubMed  Google Scholar 

Schwartz LB. Diagnostic value of tryptase in anaphylaxis and mastocytosis. Immunol Allergy Clin North Am. 2006;26:451–63.

Article  PubMed  Google Scholar 

Lin RY, Schwartz LB, Curry A, Pesola GR, Knight RJ, Lee HS, et al. Histamine and tryptase levels in patients with acute allergic reactions: An emergency department-based study. J Allergy Clin Immunol. 2000;106:65–71.

Article  CAS  PubMed  Google Scholar 

• Schwartz LB, Yunginger JW, Miller J, Bokhari R, Dull D. Time course of appearance and disappearance of human mast cell tryptase in the circulation after anaphylaxis. J Clin Invest. 1989;83:1551–5. Detailed analysis of the time course of serum tryptase levels before, during, and after an anaphylactic event in patients suffering from anaphylaxis.

Article  CAS  PubMed  PubMed Central  Google Scholar 

• Akin C, Valent P, Metcalfe DD. Mast cell activation syndrome: Proposed diagnostic criteria. J Allergy Clin Immunol. 2010;126:1099–104. This manuscript presents a first proposal for diagnostic criteria and a classification of mast cell activation syndromes.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hamilton MJ, Hornick JL, Akin C, Castells MC, Greenberger NJ. Mast cell activation syndrome: a newly recognized disorder with systemic clinical manifestations. J Allergy Clin Immunol. 2011;128:147-52.e2.

Article  PubMed  Google Scholar 

•• Valent P, Akin C, Arock M, Brockow K, Butterfield JH, Carter MC, et al. Definitions, criteria and global classification of mast cell disorders with special reference to mast cell activation syndromes: a consensus proposal. Int Arch Allergy Immunol. 2012;157:215–25. This manuscript provides definitions, diagnostic criteria, and a classification of mast cell activation syndromes in a consensus proposal.

Article  PubMed  Google Scholar 

Valent P. Mast cell activation syndromes: definition and classification. Allergy. 2013;68:417–24.

Article  CAS  PubMed  Google Scholar 

Valent P, Akin C, Bonadonna P, Hartmann K, Brockow K, Niedoszytko M, et al. Proposed diagnostic algorithm for patients with suspected mast cell activation syndrome. J Allergy Clin Immunol Pract. 2019;7:1125-33.e1.

Article  PubMed  PubMed Central  Google Scholar 

• Valent P, Hartmann K, Bonadonna P, Gülen T, Brockow K, Alvarez-Twose I, et al. Global classification of mast cell activation disorders: an ICD-10-CM-adjusted proposal of the ECNM-AIM consortium. J Allergy Clin Immunol Pract. 2022;10:1941–50. This manuscript provides a global classification and diagnostic criteria for mast cell activation disorders, including mast cell activation syndromes (MCAS) and mast cell activation disorders/conditions in which MCAS criteria are not fulfilled.

Article  CAS  PubMed  Google Scholar 

Butterfield JH. Increased excretion of mast cell mediator metabolites during mast cell activation syndrome. J Allergy Clin Immunol Pract. 2023;11:2542–6.

Article  CAS  PubMed  Google Scholar 

Chollet MB, Akin C. Hereditary alpha tryptasemia is not associated with specific clinical phenotypes. J Allergy Clin Immunol. 2022;149:728-35.e2.

Comments (0)

No login
gif