Clinical Approach to a Patient with Elevated Serum Tryptase: Implications of Acute Versus Basally Elevated Levels

  • Jonathan J. LyonsEmail author
  • Lawrence B. Schwartz


Measurement of tryptase is a valuable tool in the evaluation of patients with mast cell-related disorders and reactions. Recent advances in our understanding of a common genetic cause underlying elevated basal serum tryptase levels in the general population have provided additional context to evaluate patients with elevated serum tryptase levels. This chapter will provide an overview of tryptase, inherited and acquired causes for basal elevations of serum tryptase, and clinical applications of this biomarker in diagnosis and risk stratification of patients.


Hereditary alpha tryptasemia Mast cell activation BST Anaphylaxis Mastocytosis 



Acute myeloid leukemia


Basal serum tryptase


Chronic myeloid leukemia


Chronic spontaneous urticaria


FIP1-like-1/platelet-derived growth factor receptor-α fusion gene


GATA binding protein 2




Hereditary alpha tryptasemia


Hypereosinophilic syndrome


Janus kinase 2 gene


Juvenile myelomonocytic leukemia


KIT proto-oncogene receptor tyrosine kinase


Platelet-activating factor


Protease activated receptor


Phospholipase C gamma 2 gene


Serine protease 22 gene


Recombinant human stem cell factor


Tryptase alpha/beta 1 gene


Tryptase beta 2 gene


Tryptase delta 1 gene


Tryptase gamma 1 gene



This research was supported in part by the Division of Intramural Research of the National Institute of Allergy and Infectious Diseases, NIH.


  1. 1.
    Castells MC, Irani AM, Schwartz LB. Evaluation of human peripheral blood leukocytes for mast cell tryptase. J Immunol. 1987;138(7):2184–9.PubMedGoogle Scholar
  2. 2.
    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(6):1086–92.PubMedCrossRefGoogle Scholar
  3. 3.
    Schwartz LB, Irani AM, Roller K, Castells MC, Schechter NM. Quantitation of histamine, tryptase, and chymase in dispersed human T and TC mast cells. J Immunol. 1987;138(8):2611–5.PubMedGoogle Scholar
  4. 4.
    Sakai K, Ren S, Schwartz LB. A novel heparin-dependent processing pathway for human tryptase. Autocatalysis followed by activation with dipeptidyl peptidase I. J Clin Invest. 1996;97(4):988–95.PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    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(11):5667–73.PubMedCrossRefGoogle Scholar
  6. 6.
    Trivedi NN, Tong Q, Raman K, Bhagwandin VJ, Caughey GH. Mast cell alpha and beta tryptases changed rapidly during primate speciation and evolved from gamma-like transmembrane peptidases in ancestral vertebrates. J Immunol. 2007;179(9):6072–9.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Caughey GH. Tryptase genetics and anaphylaxis. J Allergy Clin Immunol. 2006;117(6):1411–4.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Trivedi NN, Tamraz B, Chu C, Kwok PY, Caughey GH. Human subjects are protected from mast cell tryptase deficiency despite frequent inheritance of loss-of-function mutations. J Allergy Clin Immunol. 2009;124(5):1099–105.e1–4.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    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(5):1551–5.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Schwartz LB. Diagnostic value of tryptase in anaphylaxis and mastocytosis. Immunol Allergy Clin North Am. 2006;26(3):451–63.PubMedCrossRefGoogle Scholar
  11. 11.
    He S, Peng Q, Walls AF. Potent induction of a neutrophil and eosinophil-rich infiltrate in vivo by human mast cell tryptase: selective enhancement of eosinophil recruitment by histamine. J Immunol. 1997;159(12):6216–25.PubMedGoogle Scholar
  12. 12.
    Fajardo I, Pejler G. Human mast cell beta-tryptase is a gelatinase. J Immunol. 2003;171(3):1493–9.PubMedCrossRefGoogle Scholar
  13. 13.
    Lohi J, Harvima I, Keski-Oja J. Pericellular substrates of human mast cell tryptase: 72,000 dalton gelatinase and fibronectin. J Cell Biochem. 1992;50(4):337–49.PubMedCrossRefGoogle Scholar
  14. 14.
    Brown JK, Tyler CL, Jones CA, Ruoss SJ, Hartmann T, Caughey GH. Tryptase, the dominant secretory granular protein in human mast cells, is a potent mitogen for cultured dog tracheal smooth muscle cells. Am J Respir Cell Mol Biol. 1995;13(2):227–36.PubMedCrossRefGoogle Scholar
  15. 15.
    Ruoss SJ, Hartmann T, Caughey GH. Mast cell tryptase is a mitogen for cultured fibroblasts. J Clin Invest. 1991;88(2):493–9.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Blair RJ, Meng H, Marchese MJ, Ren S, Schwartz LB, Tonnesen MG, et al. Human mast cells stimulate vascular tube formation. Tryptase is a novel, potent angiogenic factor. J Clin Invest. 1997;99(11):2691–700.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Cairns JA, Walls AF. Mast cell tryptase is a mitogen for epithelial cells. Stimulation of IL-8 production and intercellular adhesion molecule-1 expression. J Immunol. 1996;156(1):275–83.PubMedGoogle Scholar
  18. 18.
    Corvera CU, Dery O, McConalogue K, Gamp P, Thoma M, Al-Ani B, et al. Thrombin and mast cell tryptase regulate guinea-pig myenteric neurons through proteinase-activated receptors-1 and -2. J Physiol. 1999;517(Pt 3):741–56.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Schwartz LB, Bradford TR, Littman BH, Wintroub BU. The fibrinogenolytic activity of purified tryptase from human lung mast cells. J Immunol. 1985;135(4):2762–7.PubMedGoogle Scholar
  20. 20.
    Thomas VA, Wheeless CJ, Stack MS, Johnson DA. Human mast cell tryptase fibrinogenolysis: kinetics, anticoagulation mechanism, and cell adhesion disruption. Biochemistry. 1998;37(8):2291–8.PubMedCrossRefGoogle Scholar
  21. 21.
    Kozik A, Moore RB, Potempa J, Imamura T, Rapala-Kozik M, Travis J. A novel mechanism for bradykinin production at inflammatory sites. Diverse effects of a mixture of neutrophil elastase and mast cell tryptase versus tissue and plasma kallikreins on native and oxidized kininogens. J Biol Chem. 1998;273(50):33224–9.PubMedCrossRefGoogle Scholar
  22. 22.
    Maier M, Spragg J, Schwartz LB. Inactivation of human high molecular weight kininogen by human mast cell tryptase. J Immunol. 1983;130(5):2352–6.PubMedGoogle Scholar
  23. 23.
    Schwartz LB, Maier M, Spragg J. Interaction of human low molecular weight kininogen with human mast cell tryptase. Adv Exp Med Biol. 1986;198 Pt A:105–11.Google Scholar
  24. 24.
    Gruber BL, Marchese MJ, Suzuki K, Schwartz LB, Okada Y, Nagase H, et al. Synovial procollagenase activation by human mast cell tryptase dependence upon matrix metalloproteinase 3 activation. J Clin Invest. 1989;84(5):1657–62.PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Fukuoka Y, Xia HZ, Sanchez-Munoz LB, Dellinger AL, Escribano L, Schwartz LB. Generation of anaphylatoxins by human beta-tryptase from C3, C4, and C5. J Immunol. 2008;180(9):6307–16.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Lefrancais E, Duval A, Mirey E, Roga S, Espinosa E, Cayrol C, et al. Central domain of IL-33 is cleaved by mast cell proteases for potent activation of group-2 innate lymphoid cells. Proc Natl Acad Sci U S A. 2014;111(43):15502–7.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Molino M, Barnathan ES, Numerof R, Clark J, Dreyer M, Cumashi A, et al. Interactions of mast cell tryptase with thrombin receptors and PAR-2. J Biol Chem. 1997;272(7):4043–9.PubMedCrossRefGoogle Scholar
  28. 28.
    Oh SW, Pae CI, Lee DK, Jones F, Chiang GK, Kim HO, et al. Tryptase inhibition blocks airway inflammation in a mouse asthma model. J Immunol. 2002;168(4):1992–2000.PubMedCrossRefGoogle Scholar
  29. 29.
    Krishna MT, Chauhan A, Little L, Sampson K, Hawksworth R, Mant T, et al. Inhibition of mast cell tryptase by inhaled APC 366 attenuates allergen-induced late-phase airway obstruction in asthma. J Allergy Clin Immunol. 2001;107(6):1039–45.PubMedCrossRefGoogle Scholar
  30. 30.
    Tremaine WJ, Brzezinski A, Katz JA, Wolf DC, Fleming TJ, Mordenti J, et al. Treatment of mildly to moderately active ulcerative colitis with a tryptase inhibitor (APC 2059): an open-label pilot study. Aliment Pharmacol Ther. 2002;16(3):407–13.PubMedCrossRefGoogle Scholar
  31. 31.
    Imamura T, Dubin A, Moore W, Tanaka R, Travis J. Induction of vascular permeability enhancement by human tryptase: dependence on activation of prekallikrein and direct release of bradykinin from kininogens. Lab Invest. 1996;74(5):861–70.PubMedGoogle Scholar
  32. 32.
    Schwartz LB, Kawahara MS, Hugli TE, Vik D, Fearon DT, Austen KF. Generation of C3a anaphylatoxin from human C3 by human mast cell tryptase. J Immunol. 1983;130(4):1891–5.PubMedGoogle Scholar
  33. 33.
    Fellinger C, Hemmer W, Wohrl S, Sesztak-Greinecker G, Jarisch R, Wantke F. Clinical characteristics and risk profile of patients with elevated baseline serum tryptase. Allergol Immunopathol (Madr). 2014;42(6):544–52.CrossRefGoogle Scholar
  34. 34.
    Gonzalez-Quintela A, Vizcaino L, Gude F, Rey J, Meijide L, Fernandez-Merino C, et al. Factors influencing serum total tryptase concentrations in a general adult population. Clin Chem Lab Med. 2010;48(5):701–6.PubMedCrossRefGoogle Scholar
  35. 35.
    Lyons JJ, Yu X, Hughes JD, Le QT, Jamil A, Bai Y, et al. Elevated basal serum tryptase identifies a multisystem disorder associated with increased TPSAB1 copy number. Nat Genet. 2016;48(12):1564–9.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Sabato V, Chovanec J, Faber M, Milner JD, Ebo D, Lyons JJ. First identification of an inherited TPSAB1 quintuplication in a patient with clonal mast cell disease. J Clin Immunol. 2018;38(4):457–9.PubMedCrossRefGoogle Scholar
  37. 37.
    Lyons JJ. Hereditary alpha tryptasemia: genotyping and associated clinical features. Immunol Allergy Clin North Am. 2018;38(3):483–95.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Lyons JJ, Sun G, Stone KD, Nelson C, Wisch L, O’Brien M, et al. Mendelian inheritance of elevated serum tryptase associated with atopy and connective tissue abnormalities. J Allergy Clin Immunol. 2014;133(5):1471–4.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Akin C. Mast cell activation syndromes. J Allergy Clin Immunol. 2017;140(2):349–55.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Lee JK, Whittaker SJ, Enns RA, Zetler P. Gastrointestinal manifestations of systemic mastocytosis. World J Gastroenterol. 2008;14(45):7005–8.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Theoharides TC, Valent P, Akin C. Mast cells, mastocytosis, and related disorders. N Engl J Med. 2015;373(2):163–72.PubMedCrossRefGoogle Scholar
  42. 42.
    Schussler E, Yang A, Lyons JJ, Milner JD, Wang J. Persistent tryptase elevation in a patient with Gaucher disease. J Allergy Clin Immunol Pract. 2018;6(2):697–9.PubMedCrossRefGoogle Scholar
  43. 43.
    Desai A, Sowerwine K, Liu Y, Lawrence MG, Chovanec J, Hsu AP, O’Connell MP, Kim J, Boris L, Jones N, Wisch L, Eisch RR, Carter MC, Komarow HD, Zerbe C, Milner JD, Maric I, Sun X, Lee CR, Tunc I, Pirooznia M, Stone KD, Holland SM, Metcalfe DD, Lyons JJ. GATA2-deficient mast cells limit IgE-mediated immediate hypersensitivity reactions in humans. J Allergy Clin Immunol. 2019;144(2):613–7. Scholar
  44. 44.
    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(26):1622–6.CrossRefPubMedGoogle Scholar
  45. 45.
    Valent P, Akin C, Metcalfe DD. Mastocytosis: 2016 updated WHO classification and novel emerging treatment concepts. Blood. 2017;129(11):1420–7.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Pardanani A, Chen D, Abdelrahman RA, Reichard KK, Zblewski D, Wood AJ, et al. Clonal mast cell disease not meeting WHO criteria for diagnosis of mastocytosis: clinicopathologic features and comparison with indolent mastocytosis. Leukemia. 2013;27(10):2091–4.PubMedCrossRefGoogle Scholar
  47. 47.
    Bonadonna P, Zanotti R, Muller U. Mastocytosis and insect venom allergy. Curr Opin Allergy Clin Immunol. 2010;10(4):347–53.PubMedCrossRefGoogle Scholar
  48. 48.
    Brockow K, Jofer C, Behrendt H, Ring J. Anaphylaxis in patients with mastocytosis: a study on history, clinical features and risk factors in 120 patients. Allergy. 2008;63(2):226–32.CrossRefPubMedGoogle Scholar
  49. 49.
    Gulen T, Hagglund H, Dahlen B, Nilsson G. High prevalence of anaphylaxis in patients with systemic mastocytosis – a single-centre experience. Clin Exp Allergy. 2014;44(1):121–9.CrossRefPubMedGoogle Scholar
  50. 50.
    Wood RA, Camargo CA Jr, Lieberman P, Sampson HA, Schwartz LB, Zitt M, et al. Anaphylaxis in America: the prevalence and characteristics of anaphylaxis in the United States. J Allergy Clin Immunol. 2014;133(2):461–7.PubMedCrossRefGoogle Scholar
  51. 51.
    Sheikh A, Hippisley-Cox J, Newton J, Fenty J. Trends in national incidence, lifetime prevalence and adrenaline prescribing for anaphylaxis in England. J R Soc Med. 2008;101(3):139–43.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Klion AD, Noel P, Akin C, Law MA, Gilliland DG, Cools J, et al. Elevated serum tryptase levels identify a subset of patients with a myeloproliferative variant of idiopathic hypereosinophilic syndrome associated with tissue fibrosis, poor prognosis, and imatinib responsiveness. Blood. 2003;101(12):4660–6.PubMedCrossRefGoogle Scholar
  53. 53.
    Gotlib J, Akin C. Mast cells and eosinophils in mastocytosis, chronic eosinophilic leukemia, and non-clonal disorders. Semin Hematol. 2012;49(2):128–37.PubMedCrossRefGoogle Scholar
  54. 54.
    Maric I, Robyn J, Metcalfe DD, Fay MP, Carter M, Wilson T, et al. KIT D816V-associated systemic mastocytosis with eosinophilia and FIP1L1/PDGFRA-associated chronic eosinophilic leukemia are distinct entities. J Allergy Clin Immunol. 2007;120(3):680–7.PubMedCrossRefGoogle Scholar
  55. 55.
    Schwaab J, Umbach R, Metzgeroth G, Naumann N, Jawhar M, Sotlar K, et al. KIT D816V and JAK2 V617F mutations are seen recurrently in hypereosinophilia of unknown significance. Am J Hematol. 2015;90(9):774–7.PubMedCrossRefGoogle Scholar
  56. 56.
    Ogbogu PU, Bochner BS, Butterfield JH, Gleich GJ, Huss-Marp J, Kahn JE, et al. Hypereosinophilic syndrome: a multicenter, retrospective analysis of clinical characteristics and response to therapy. J Allergy Clin Immunol. 2009;124(6):1319–25.. e3PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    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(5):683–90.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    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 haematology. Eur J Clin Invest. 2009;39(10):914–23.PubMedCrossRefGoogle Scholar
  59. 59.
    Sperr WR, Jordan JH, Baghestanian M, Kiener HP, Samorapoompichit P, Semper H, et al. Expression of mast cell tryptase by myeloblasts in a group of patients with acute myeloid leukemia. Blood. 2001;98(7):2200–9.PubMedCrossRefGoogle Scholar
  60. 60.
    Ichikawa H, Tanabe K, Mizushima H, Hayashi Y, Mizutani S, Ishii E, et al. Common gene expression signatures in t(8;21)- and inv(16)-acute myeloid leukaemia. Br J Haematol. 2006;135(3):336–47.PubMedCrossRefGoogle Scholar
  61. 61.
    Sonneck K, Florian S, Bohm A, Krauth MT, Kondo R, Hauswirth AW, et al. Evaluation of biologic activity of tryptase secreted from blast cells in acute myeloid leukemia. Leuk Lymphoma. 2006;47(5):897–906.PubMedCrossRefGoogle Scholar
  62. 62.
    Bresolin S, Zecca M, Flotho C, Trentin L, Zangrando A, Sainati L, et al. Gene expression-based classification as an independent predictor of clinical outcome in juvenile myelomonocytic leukemia. J Clin Oncol. 2010;28(11):1919–27.PubMedCrossRefGoogle Scholar
  63. 63.
    Frank O, Brors B, Fabarius A, Li L, Haak M, Merk S, et al. Gene expression signature of primary imatinib-resistant chronic myeloid leukemia patients. Leukemia. 2006;20(8):1400–7.PubMedCrossRefGoogle Scholar
  64. 64.
    Sperr WR, Mitterbauer M, Mitterbauer G, Kundi M, Jager U, Lechner K, et al. Quantitation of minimal residual disease in acute myeloid leukemia by tryptase monitoring identifies a group of patients with a high risk of relapse. Clin Cancer Res. 2005;11(18):6536–43.PubMedCrossRefGoogle Scholar
  65. 65.
    Sperr WR, Pfeiffer T, Hoermann G, Herndlhofer S, Sillaber C, Mannhalter C, et al. Serum-tryptase at diagnosis: a novel biomarker improving prognostication in Ph(+) CML. Am J Cancer Res. 2015;5(1):354–62.PubMedGoogle Scholar
  66. 66.
    Min HK, Moxley G, Neale MC, Schwartz LB. Effect of sex and haplotype on plasma tryptase levels in healthy adults. J Allergy Clin Immunol. 2004;114(1):48–51.PubMedCrossRefGoogle Scholar
  67. 67.
    Fenger RV, Linneberg A, Vidal C, Vizcaino L, Husemoen LL, Aadahl M, et al. Determinants of serum tryptase in a general population: the relationship of serum tryptase to obesity and asthma. Int Arch Allergy Immunol. 2012;157(2):151–8.PubMedCrossRefGoogle Scholar
  68. 68.
    Dugas-Breit S, Schopf P, Dugas M, Schiffl H, Rueff F, Przybilla B. Baseline serum levels of mast cell tryptase are raised in hemodialysis patients and associated with severity of pruritus. J Dtsch Dermatol Ges. 2005;3(5):343–7.PubMedCrossRefGoogle Scholar
  69. 69.
    Sirvent AE, Gonzalez C, Enriquez R, Fernandez J, Millan I, Barber X, et al. Serum tryptase levels and markers of renal dysfunction in a population with chronic kidney disease. J Nephrol. 2010;23(3):282–90.PubMedPubMedCentralGoogle Scholar
  70. 70.
    Doong JC, Chichester K, Oliver ET, Schwartz LB, Saini SS. Chronic idiopathic urticaria: systemic complaints and their relationship with disease and immune measures. J Allergy Clin Immunol Pract. 2017;5(5):1314–8.PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Siles R, Xu M, Hsieh FH. The utility of serum tryptase as a marker in chronic spontaneous urticaria. Acta Derm Venereol. 2013;93(3):354–5.PubMedCrossRefGoogle Scholar
  72. 72.
    Cooper PJ, Schwartz LB, Irani AM, Awadzi K, Guderian RH, Nutman TB. Association of transient dermal mastocytosis and elevated plasma tryptase levels with development of adverse reactions after treatment of onchocerciasis with ivermectin. J Infect Dis. 2002;186(9):1307–13.PubMedCrossRefGoogle Scholar
  73. 73.
    Rajamanickam A, Munisankar S, Bhootra Y, Dolla CK, Nutman TB, Babu S. Elevated systemic levels of eosinophil, neutrophil, and mast cell granular proteins in Strongyloides Stercoralis infection that diminish following treatment. Front Immunol. 2018;9:207.PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Moskowitz CH, Stiff P, Gordon MS, McNiece I, Ho AD, Costa JJ, et al. Recombinant methionyl human stem cell factor and filgrastim for peripheral blood progenitor cell mobilization and transplantation in non-Hodgkin’s lymphoma patients–results of a phase I/II trial. Blood. 1997;89(9):3136–47.PubMedGoogle Scholar
  75. 75.
    Costa JJ, Demetri GD, Harrist TJ, Dvorak AM, Hayes DF, Merica EA, et al. Recombinant human stem cell factor (kit ligand) promotes human mast cell and melanocyte hyperplasia and functional activation in vivo. J Exp Med. 1996;183(6):2681–6.PubMedCrossRefGoogle Scholar
  76. 76.
    Metcalfe DD. Mast cells and mastocytosis. Blood. 2008;112(4):946–56.PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Schwartz LB. Tryptase: a mast cell serine protease. Methods Enzymol. 1994;244:88–100.PubMedCrossRefGoogle Scholar
  78. 78.
    Vadas P, Gold M, Perelman B, Liss GM, Lack G, Blyth T, et al. Platelet-activating factor, PAF acetylhydrolase, and severe anaphylaxis. N Engl J Med. 2008;358(1):28–35.PubMedCrossRefGoogle Scholar
  79. 79.
    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(3):215–25.CrossRefPubMedGoogle Scholar
  80. 80.
    Sala-Cunill A, Cardona V, Labrador-Horrillo M, Luengo O, Esteso O, Garriga T, et al. Usefulness and limitations of sequential serum tryptase for the diagnosis of anaphylaxis in 102 patients. Int Arch Allergy Immunol. 2013;160(2):192–9.CrossRefPubMedGoogle Scholar
  81. 81.
    Vadas P, Perelman B, Liss G. Platelet-activating factor, histamine, and tryptase levels in human anaphylaxis. J Allergy Clin Immunol. 2013;131(1):144–9.PubMedCrossRefGoogle Scholar
  82. 82.
    Golden DB. Patterns of anaphylaxis: acute and late phase features of allergic reactions. Novartis Found Symp. 2004;257:101–10; discussion 10–5, 57–60, 276–85.Google Scholar
  83. 83.
    Dua S, Dowey J, Foley L, Islam S, King Y, Ewan P, et al. Diagnostic value of tryptase in food allergic reactions: a prospective study of 160 adult peanut challenges. J Allergy Clin Immunol Pract. 2018;6(5):1692–8.e1.PubMedCrossRefGoogle Scholar
  84. 84.
    Wongkaewpothong P, Pacharn P, Sripramong C, Boonchoo S, Piboonpocanun S, Visitsunthorn N, et al. The utility of serum tryptase in the diagnosis of food-induced anaphylaxis. Allergy Asthma Immunol Res. 2014;6(4):304–9.PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Aniceto V, Dias MM, Melo JML, Trevisan-Neto O, Aragon DC, Maia LSM, et al. Serum baseline tryptase level as a marker for the severity of anaphylaxis. Int Arch Allergy Immunol. 2019;179:201–8.PubMedCrossRefGoogle Scholar
  86. 86.
    Haeberli G, Bronnimann M, Hunziker T, Muller U. Elevated basal serum tryptase and hymenoptera venom allergy: relation to severity of sting reactions and to safety and efficacy of venom immunotherapy. Clin Exp Allergy. 2003;33(9):1216–20.CrossRefPubMedGoogle Scholar
  87. 87.
    Rueff F, Przybilla B, Bilo MB, Muller U, Scheipl F, Aberer W, et al. Predictors of severe systemic anaphylactic reactions in patients with Hymenoptera venom allergy: importance of baseline serum tryptase-a study of the European Academy of Allergology and Clinical Immunology Interest Group on Insect Venom Hypersensitivity. J Allergy Clin Immunol. 2009;124(5):1047–54.CrossRefPubMedGoogle Scholar
  88. 88.
    Kucharewicz I, Bodzenta-Lukaszyk A, Szymanski W, Mroczko B, Szmitkowski M. Basal serum tryptase level correlates with severity of hymenoptera sting and age. J Investig Allergol Clin Immunol. 2007;17(2):65–9.PubMedGoogle Scholar
  89. 89.
    Sahiner UM, Yavuz ST, Buyuktiryaki B, Cavkaytar O, Yilmaz EA, Tuncer A, et al. Serum basal tryptase may be a good marker for predicting the risk of anaphylaxis in children with food allergy. Allergy. 2014;69(2):265–8.PubMedCrossRefGoogle Scholar
  90. 90.
    Akin C, Scott LM, Kocabas CN, Kushnir-Sukhov N, Brittain E, Noel P, et al. Demonstration of an aberrant mast-cell population with clonal markers in a subset of patients with “idiopathic” anaphylaxis. Blood. 2007;110(7):2331–3.PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Carter MC, Desai A, Komarow HD, Bai Y, Clayton ST, Clark AS, et al. A distinct biomolecular profile identifies monoclonal mast cell disorders in patients with idiopathic anaphylaxis. J Allergy Clin Immunol. 2018;141(1):180–8.e3.PubMedCrossRefGoogle Scholar
  92. 92.
    Aberer E, Savic S, Bretterklieber A, Reiter H, Berghold A, Aberer W. Disease spectrum in patients with elevated serum tryptase levels. Australas J Dermatol. 2015;56(1):7–13.PubMedCrossRefGoogle Scholar
  93. 93.
    Brockow K. Epidemiology, prognosis, and risk factors in mastocytosis. Immunol Allergy Clin North Am. 2014;34(2):283–95.PubMedCrossRefGoogle Scholar
  94. 94.
    Sargur R, Cowley D, Murng S, Wild G, Green K, Shrimpton A, et al. Raised tryptase without anaphylaxis or mastocytosis: heterophilic antibody interference in the serum tryptase assay. Clin Exp Immunol. 2011;163(3):339–45.PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Schliemann S, Seyfarth F, Hipler UC, Elsner P. Impact of age and heterophilic interference on the basal serum tryptase, a risk indication for anaphylaxis, in 1,092 dermatology patients. Acta Derm Venereol. 2012;92(5):484–9.PubMedCrossRefGoogle Scholar
  96. 96.
    van Toorenenbergen AW, Hooijkaas H, Heerenbrink GK, Dufour-van den Goorbergh DM Heterophilic antibody interference in a tryptase immunoassay. Clin Biochem 2008;41(4–5):331–334.Google Scholar
  97. 97.
    van Toorenenbergen AW, van Daele PL, Boonstra JG. False-elevated serum tryptase assay result caused by heterophilic antibodies. J Allergy Clin Immunol. 2005;116(5):1159–60.PubMedCrossRefGoogle Scholar
  98. 98.
    Foster B, Schwartz LB, Devouassoux G, Metcalfe DD, Prussin C. Characterization of mast-cell tryptase-expressing peripheral blood cells as basophils. J Allergy Clin Immunol. 2002;109(2):287–93.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of HealthBethesdaUSA
  2. 2.Department of Internal MedicineVirginia Commonwealth UniversityRichmondUSA

Personalised recommendations