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.

Article  CAS  PubMed  Google Scholar 

• Maun HR, Jackman JK, Choy DF, Loyet KM, Staton TL, Jia G, et al. An allosteric anti-tryptase antibody for the treatment of mast cell-mediated severe asthma. Cell. 2019;179(2):417–31 e19. First study to demonstrate the impact of blocking human tryptase in an in vivo anaphylaxis model.

Caughey GH. Tryptase genetics and anaphylaxis. J Aller Clin Immunol. 2006;117(6):1411–4.

Article  CAS  Google Scholar 

Pereira PJ, Bergner A, Macedo-Ribeiro S, Huber R, Matschiner G, Fritz H, et al. Human beta-tryptase is a ring-like tetramer with active sites facing a central pore. Nature. 1998;392(6673):306–11.

Article  CAS  PubMed  ADS  Google Scholar 

•• Le QT, Lyons JJ, Naranjo AN, Olivera A, Lazarus RA, Metcalfe DD, et al. Impact of naturally forming human alpha/beta-tryptase heterotetramers in the pathogenesis of hereditary alpha-tryptasemia. J Exp Med. 2019;216(10):2348–61. First demonstration of naturally forming heterotetrameric tryptases and their unique activities in vitro.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yu Y, Blokhuis BR, Garssen J, Redegeld FA. Non-IgE mediated mast cell activation. Eur J Pharmacol. 2016;778:33–43.

Article  CAS  PubMed  Google Scholar 

Krystel-Whittemore M, Dileepan KN, Wood JG. Mast cell: a multi-functional master cell. Front Immunol. 2015;6:620.

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(6):2702–10.

Article  CAS  PubMed  PubMed Central  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(11):5667–73.

Article  CAS  PubMed  Google Scholar 

Akin C, Soto D, Brittain E, Chhabra A, Schwartz LB, Caughey GH, Metcalfe DD. Tryptase haplotype in mastocytosis: relationship to disease variant and diagnostic utility of total tryptase levels. Clin Immunol. 2007;123(3):268–71.

Article  CAS  PubMed  PubMed Central  Google Scholar 

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 Aller Immunol. 2019;179(3):201–8.

Article  CAS  Google Scholar 

Enrique E, García-Ortega P, Gaig P, Richart C, Sotorra O. Usefulness of UniCAP-tryptase fluoroimmunoassay in the diagnosis of anaphylaxis. Allergy. 1999;54(6):602–6.

Article  CAS  PubMed  Google Scholar 

Schwartz LB. Diagnostic value of tryptase in anaphylaxis and mastocytosis. Immunol Aller Clin North Am. 2006;26(3):451–63.

Article  Google Scholar 

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.

Article  CAS  PubMed  Google Scholar 

Gulen T, Hagglund H, Dahlen B, Nilsson G. High prevalence of anaphylaxis in patients with systemic mastocytosis - a single-centre experience. Clin Exp Aller. 2014;44(1):121–9.

Article  CAS  Google Scholar 

Greiner G, Sprinzl B, Górska A, Ratzinger F, Gurbisz M, Witzeneder N, et al. Hereditary α tryptasemia is a valid genetic biomarker for severe mediator-related symptoms in mastocytosis. Blood. 2021;137(2):238–47.

Article  CAS  PubMed  Google Scholar 

Wu R, Lyons JJ. Hereditary alpha-tryptasemia: a commonly inherited modifier of anaphylaxis. Curr Aller Asthma Rep. 2021;21(5):33.

Article  CAS  Google Scholar 

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.

Article  CAS  PubMed  PubMed Central  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(9):1796–810. First cloning of the duplicated human tryptase locus and generated a model for what the upper limit of serum tryptase levels are based upon TPSAB1 replication number.

Article  CAS  PubMed  Google Scholar 

Luskin KT, White AA, Lyons JJ. The genetic basis and clinical impact of hereditary alpha-tryptasemia. J Aller Clin Immunol Pract. 2021;9(6):2235–42.

Article  CAS  Google Scholar 

Lyons JJ, Yi T. Mast cell tryptases in allergic inflammation and immediate hypersensitivity. Curr Opin Immunol. 2021;72:94–106.

Article  CAS  PubMed  Google Scholar 

Lyons JJ. Hereditary alpha tryptasemia: genotyping and associated clinical features. Immunol Aller Clin North Am. 2018;38(3):483–95.

Article  Google Scholar 

Sperr WR, Jordan J-H, 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 Aller Immunol. 2002;128(2):136–41.

Article  CAS  Google Scholar 

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 Aller. 2003;33(9):1216–20.

Article  CAS  Google Scholar 

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.

CAS  PubMed  Google Scholar 

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 Aller Clin Immunol. 2009;124(5):1047–54.

Article  CAS  Google Scholar 

Guenova E, Volz T, Eichner M, Hoetzenecker W, Caroli U, Griesinger G, et al. Basal serum tryptase as risk assessment for severe Hymenoptera sting reactions in elderly. Allergy. 2010;65(7):919–23.

Article  CAS  PubMed  Google Scholar 

Sahiner UM, Yavuz ST, Buyuktiryaki B, Cavkaytar O, Yilmaz EA, Tuncer A, Sackesen C. 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.

Article  CAS  PubMed  Google Scholar 

Srivastava S, Huissoon AP, Barrett V, Hackett S, Dorrian S, Cooke MW, Krishna MT. Systemic reactions and anaphylaxis with an acute serum tryptase ≥14 μg/L: retrospective characterisation of aetiology, severity and adherence to National Institute of Health and Care Excellence (NICE) guidelines for serial tryptase measurements and specialist referral. J Clin Pathol. 2014;67(7):614–9.

Article  PubMed  Google Scholar 

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.

Article  PubMed  Google Scholar 

Dua S, Dowey J, Foley L, Islam S, King Y, Ewan P, Clark AT. Diagnostic value of tryptase in food allergic reactions: a prospective study of 160 adult peanut challenges. J Aller Clin Immunol Pract. 2018;6(5):1692-8.e1.

Article  Google Scholar 

• Lang A, Kubala S, Grieco MC, Mateja A, Pongracic J, Liu Y, et al. Severe food allergy reactions are associated with α-tryptase. J Aller Clin Immunol. 2023;152(4):933–9. First study to demonstrate the impact of alpha-tryptase on food allergic reaction severity.

Article  CAS  Google Scholar 

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.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lyons JJ. Inherited and acquired determinants of serum tryptase levels in humans. Ann Allergy Asthma Immunol. 2021;127(4):420–6.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Marquardt U, Zettl F, Huber R, Bode W, Sommerhoff C. The crystal structure of human alpha1-tryptase reveals a blocked substrate-binding region. J Mol Biol. 2002;321(3):491–502.

Article  CAS  PubMed  Google Scholar 

•• Lyons JJ, Chovanec J, O’Connell MP, Liu Y, Šelb J, Zanotti R, et al. Heritable risk for severe anaphylaxis associated with increased α-tryptase-encoding germline copy number at TPSAB1 J Allergy Clin Immunol. 2021;147(2):622-32. First study to link HaT with mastocytosis, venom allergy, and idiopathic anaphylaxis.

Boyden SE, Desai A, Cruse G, Young ML, Bolan HC, Scott LM, et al. Vibratory urticaria associated with a missense variant in ADGRE2. N Engl J Med. 2016;374(7):656–63.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Brockow K. Epidemiology, prognosis, and risk factors in mastocytosis. Immunol Aller Clin North Am. 2014;34(2):283–95.

Article  Google Scholar 

Sabato V, Van De Vijver E, Hagendorens M, Vrelust I, Reyniers E, Fransen E, et al. Familial hypertryptasemia with associated mast cell activation syndrome. J Aller Clin Immunol. 2014;134(6):1448–50 e3.

Lee SE, Jeong SK, Lee SH. Protease and protease-activated receptor-2 signaling in the pathogenesis of atopic dermatitis. Yonsei Med J. 2010;51(6):808–22.

Article