Vol 9, No 4 (2023)
Review paper
Published online: 2023-09-08

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Forum Dermatologicum

2023, Vol. 9, No. 4, 133–137

DOI: 10.5603/fd.96810

Copyright © 2023 Via Medica

ISSN 2451–1501, e-ISSN 2451–151X

Hereditary alpha tryptasemia: literature overview on the genetic trait and its clinical manifestations

Agnieszka Rydz1Magdalena Lange2
1Student’s Scientific Circle Practical and Experimental Dermatology, Medical University of Gdańsk, Poland
2Department of Dermatology, Venereology and Allergology, Medical University of Gdańsk, Poland

Address for correspondence:

Agnieszka Rydz, Student’s Scientific Circle Practical
and Experimental Dermatology, Medical University
of Gdańsk, Smoluchowskiego 17, 80214 Gdańsk,
Poland; e-mail: agnieszka.rydz@gumed.edu.pl

Received: 2.08.2023 Accepted: 14.08.2023 Early publication date: 8.09.2023

Hereditary Alpha Tryptasemia (HαT) is a genetic condition characterized by an increased number of copies of the TPSAB1 gene, resulting in elevated basal serum tryptase levels and an increased risk of anaphylaxis, especially in individuals with IgE-dependent allergies or systemic mastocytosis. The severity of clinical symptoms can vary and is influenced by the number of extra TPSAB1 gene copies, suggesting a gene-dose effect. Approximately two-thirds of individuals with HαT show minimal or no symptoms. The remaining individuals with HαT may present with Hymenoptera venom allergy, flushing, urticarial/angioedema, irritable bowel syndrome, gastrointestinal reflux, hypermobility, neuropsychiatric symptoms and dysautonomia.
Recent studies revealed that α-tryptase which forms complexes with β-tryptase activate protease-activated receptor-2 (PAR2) receptors. Activation of these receptors may lead to hypotension, muscle contraction, inflammation, and trigger neuropeptide secretion, and in consequence, result in mast cell degranulation. This cycle of activation and degranulation may potentially contribute to the development of mast cell activation syndrome (MCAS).
Mast cell activation syndromes are defined by systemic, severe and recurrent mast cell activations, usually in the form of anaphylaxis. Hereditary/familial MCAS is a specific subtype of MCAS, which is associated with HαT.
Diagnostic work-up for HαT includes determination of basal serum tryptase level and the presence of additional TPSAB1 gene copies using droplet digital polymerase chain reaction.
Further research is needed, to explore the relationship between HαT and MCAS, as well as to determine if there is a distinct form of hereditary MCAS which is independent of HαT. These investigations aim to improve diagnostic approaches and treatment strategies for individuals with HαT, enhancing their management and overall quality of life.
Forum Derm. 2023; 9, 4: 133137
Keywords: hereditary alpha tryptasemia, HAT, familial/hereditary MCAS


Hereditary alpha tryptasemia (HαT) is an autosomal dominant genetic trait caused by an increased number of copies of the TPSAB1 gene, which encodes for alpha-tryptase. The estimated frequency of HαT is 35.5% within the Western and predominantly Caucasian population [1–3]. This condition, first described in 2016, is a common cause of elevated basal serum tryptase (BST) currently defined clinically as >11.4 ng/mL and is associated with var­- ious clinical symptoms [4]. HαT patients may present with systemic immediate hypersensitivity reactions, particularly Hymenoptera venom allergy, pruritus, flushing, urticarial/ /angioedema, joint hypermobility, connective tissue disorders, functional gastrointestinal diseases, neuropsychiatric symptoms, and dysautonomia [4–6]. The diversity and seve­rity of symptoms vary among affected individuals, with some experiencing milder manifestations and others displaying more pronounced symptoms. Studies have shown that the severity of symptoms in HαT patients is positively correlated with the number of TPSAB1 gene copies, which suggests a gene-dose effect [5, 6].

Individuals with HαT are at an increased risk of developing mast cell activation syndrome (MCAS) which is defined by systemic, severe and recurrent mast cell activations, usually in the form of anaphylaxis, a substantial, event-related increase of serum tryptase level beyond the individual’s baseline and a response of the symptoms to medicines directed against mast cells or antimediator therapy [7]. The association between HαT and MCAS is particularly significant when HαT coexists with IgE-dependent allergies or systemic mastocytosis (SM) [8, 9]. In such cases, the risk of anaphylaxis and severe allergic reactions is heightened [7].

The relationship between HαT and MCAS has gathered attention in the medical community, leading to the identification of a specific subtype of MCAS known as hereditary/ /familial MCAS or HαT + MCAS. In this subtype, MCAS is not attributed to any allergies or underlying clonal MC disease, but the diagnostic criteria for MCAS and HαT are met [7]. However, it is still being investigated whether a distinct form of hereditary MCAS exists independently of HαT.

This review aims to provide a comprehensive understanding of HαT including its clinical manifestations and the correlation between HαT and MCAS.


Mast cells (MCs) are bone-marrow-derived immune cells located in peripheral tissues, particularly those near the external environment, such as the skin, airways and gastrointestinal tract [6, 10, 11]. Mast cells are the main effectors in type I allergic reactions and diseases such as urticaria, asthma, anaphylaxis, rhinoconjunctivitis and allergic rhinitis [12, 13]. Mast cells are primarily activated by IgE-antigen complexes bound to the FcRI receptor on their surface. This interaction leads to the degranulation of MCs and the release of MC-derived mediators including histamine, cytokines, chemokines, and proteases inclu- ding tryptase, which is the most specific MC product [14]. The role of MCs and MC-mediators is to further activate an immune system and to provide various adaptive immune responses by affecting T-cells and lymph node activity [15].

Mast cells can be activated in different tissues. In the gastrointestinal tract, MC activation leads to increased fluid secretion, smooth muscle contraction, and peristalsis resul­ting in cramps, vomiting or diarrhoea [16]. In the respiratory tract, mast cell activation (MCA) causes airway constriction, increased mucus production, and coughing. In the skin, MC activation results mainly in the occurrence of urticaria (hives), angioedema and flushing [17].


Tryptase is a protein produced by MCs and basophils [14, 18, 19]. These cells store mature tryptases in secretory granules, where they are present as tetrameric serine protease [20]. The primary function of tryptase is its involvement in allergic inflammation, as occurs in type I immediate hypersensitivity reactions, where mature tryptases are released from MCs secretory granules with other MC-derived mediators. The proteins that have not undergone enzymatic conversion into mature tetrameric tryptases are known as protryptases [21]. These monomeric proteins are consistently secreted into the serum and constitute a significant portion of the measured BST [22].

Four types of tryptase have been identified, including three soluble forms (α, β, and δ) and one membrane-anchored form (γ) [22]. The first two isoforms are essentially unique to humans, as they have undergone important evolutionary modifications, such as duplications, gene conversions missense and nonsense mutations [22, 23].

The human tryptase locus on chromosome 16 contains four paralogous genes (TPSG1, TPSB2, TPSAB1, and TPSD1) [22]. TPSAB1 gene can produce either alpha-tryptase or beta-tryptase. On the other hand, the TPSB2 gene encodes only beta-tryptase [24, 25]. It is important to note that approximately one-third of individuals lack alpha-tryptase, while no one has been reported to lack beta-tryptase [22, 23, 26].

HαT is defined by the presence of extra copies of alpha-tryptase encoding sequences on a single allele in approximately 5% of individuals [15, 26–30]. The presence of extra copies of alpha-tryptase encoding sequences is associated with elevated basal serum tryptase (BST) levels currently defined clinically as > 11.4 ng/mL. This increase in BST levels is likely influenced by unidentified modifiers of gene expression specific to the alpha-tryptase enco­ding replications [22]. Beta-tryptase, despite its similarities, does not exhibit the same clinical effect as alpha-tryptase. Therefore, variations in beta-tryptase copy numbers alone do not lead to increased BST levels [22].


Recently, Le QT, et al. [25] conducted a study revealing that, unlike β-tryptase, α-tryptase tetramers lack protease activity. The researchers demonstrated that the expression of α-tryptase in individuals leads to the natural formation of heterotetramers, consisting of two α-tryptase and two β-tryptase protomers, known as α/β-tryptase. These α/β-tryptase complexes specifically activate protease-activated receptor-2 (PAR2), which is found in various cell types including smooth muscle, neurons, and endothelium. Stimulation of PAR2 during MC degranulation can lead to various clinical effects. For instance, in systemic anaphylaxis, activation of PAR2 on vascular endothelium may worsen hypotension [25]. In conditions like inflammatory bowel disease and asthma, PAR2 activation on smooth muscle can result in muscle contraction, further exacerbating symptoms [31, 32]. Also, activation of PAR2 on keratinocytes and sensory nerves in the skin might intensify inflammation, pruritus, and hyperalgesia [33–36]. In addition, activation of PAR2 on sensory nerves has been found to result in the secretion of neuropeptides such as Substance P and calcitonin gene-related peptides [37]. These neuropeptides then bind to specific receptors on MCs, which triggers further degranulation [13, 38]. This cycle of activation and degranulation may potentially contribute to the development of MCAS. These findings suggest that HαT is strongly connected with hereditary/familial MCAS presenting similar symptoms.

Based on Lyons JJ. Study [20], systemic immediate hypersensitivity reactions to stinging insects were found to be 20% more common among individuals with HαT. Moreover, flushing, pruritus, chronic gastroesophageal reflux, arthralgia, body pain, irritable bowel syndrome and sleep disruption were the most common complaints reported in symptomatic individuals.

The symptoms of MCA may resemble those of HαT and may vary among individuals. Typical clinical symptoms of MCA include pruritus, flushing, urticaria, angioedema, nasal congestion, wheezing, cough, diarrhoea, headache, and hypotension which may occur in various diseases [7].


The diagnosis of HαT involves several key factors as described in the Lyons study [20]. When considering HαT as a possibility, the primary indicator is BST over 8 ng/mL. This typically comes to attention following evident allergic reactions, anaphylaxis, or when diagnosing patients with hymenoptera venom allergy, mastocytosis symptoms, or certain haematologic malignancies. It’s worth noting that nearly 80% of people with the HαT trait have BST levels surpassing the upper limit of normal cited by most laboratories, which is 11.4 ng/mL.

Tryptase genotyping is necessary to confirm the trait. A droplet digital polymerase chain reaction (ddPCR) assay is employed to demonstrate an increased copy number of the TPSAB1 gene responsible for encoding alpha-tryptase [39, 40]. It’s important to mention that routine next-generation sequencing methods may not be sufficient for characterizing tryptase gene composition or copy numbers accurately [41].

In highly symptomatic individuals, further evaluation becomes crucial. While HαT is a common condition and many patients may exhibit minimal or no symptoms, it’s important to consider the possibility of coexisting disorders in those experiencing pronounced symptoms. This includes individuals displaying signs and symptoms suggestive of mastocytosis, MCAS or clonal myeloid diseases such as lymphadenopathy, hepatosplenomegaly, abnormalities in complete blood count, eosinophilic tissue infiltration, anaphylaxis (particularly hypotensive), cutaneous symptoms of mastocytosis and the presence of Darier’s sign [42, 43].

To diagnose MCAS, which can present similar clinical features, three criteria must be met [7, 44]: (a) documented evidence of typical clinical symptoms that result from recurrent acute systemic MCA, resembling episodes of recurrent anaphylaxis (b) a significant and temporary increase in MC-derived mediators (e.g., tryptase, histamine, and prostaglandin D2 metabolites) in serum and urine, which should be compared to baseline levels measured before the event or at least 24 hours after all clinical signs and symptoms have completely subsided, and (c) positive response to drugs that block MCA or inhibit MC mediators, production, or effects [7].


Pharmacotherapy is the primary approach for treating symptomatic individuals with HαT, which is similar to the treatment used for clonal mast cell disorders. The treatment involves various medications such as H1- and H2-antihistamines, MC stabilizers like compounded oral ketotifen or cromolyn sodium, leukotriene modifiers, and, in some cases, aspirin or intermittent courses of oral cortico­steroids [22].

Patients experiencing anaphylaxis should have at least two epinephrine autoinjectors and should be educated on their proper use.

In retrospective studies, omalizumab was found to improve cutaneous and respiratory symptoms connected with MCA [28, 45]. In a trial, described by Carter et al. [27], one individual with HαT who received omalizumab experienced a reduction in anaphylaxis episodes compared to one patient who received a placebo [27]. Moreover, a retrospective study conducted by Giannetti et al. [45], also reported a decrease in anaphylaxis episodes among HαT patients treated with omalizumab.

It is really important to monitor symptomatic individuals with HαT for bone loss, for the following reasons. Firstly, many clinical reports, have connected high BST levels with premature osteopenia and osteoporosis. Secondly, increased populations of bone marrow MCs and eosinophils have been observed in symptomatic individuals with HαT which may be a risk factor for early onset of bone loss. Lastly, symptomatic individuals with HαT often receive high-dose systemic corticosteroids, which can contribute to bone loss. Therefore, it is recommended to perform bone densitometry in symptomatic adult patients (both male and female) [30, 46].


In summary, HαT is a genetic condition characterized by an increased number of copies of the TPSAB1 gene, which encodes for alpha-tryptase.

HαT may manifest with a diverse range of clinical symptoms including immediate hypersensitivity reactions, allergies, pruritus (itching), flushing, joint hypermobility, connective tissue disorders, and functional gastrointestinal diseases. However, approximately two-thirds of individuals with HαT show minimal or no symptoms.

Importantly, individuals with HαT are at an increased risk of developing anaphylaxis, particularly when they have coexisting IgE-dependent allergies or systemic mastocytosis. Currently, HαT is considered a heritable modifier of both idiopathic and Hymenoptera venom anaphylaxis [1].

A specific subtype of MCAS, known as hereditary/familial MCAS or HαT + MCAS, has been identified in association with HαT.

Further research is needed to delve deeper into the relationship between HαT and MCAS to determine whether MCAS exists independently of HαT or not. These investigations aim to enhance our understanding of these conditions and improve diagnostic and treatment approaches.

Article information and declarations
Author contributions

The authors confirm their contribution to the paper as follows: study conception and design: AR, ML; data collection: AR, ML; analysis and interpretation of results: AR, ML; draft manuscript preparation: AR, ML. All authors approved the final version of the manuscript.


There was no funding.


Conflict of interest

The authors of this publication declare no conflicts of interest.

Supplementary material

There is no supplementary material.


  1. Kačar M, Rijavec M, Šelb J, et al. Clonal mast cell disorders and hereditary α-tryptasemia as risk factors for anaphylaxis. Clin Exp Allergy. 2023; 53(4): 392404, doi: 10.1111/cea.14264, indexed in Pubmed: 36654513.
  2. Lyons JJ, Yi T. Mast cell tryptases in allergic inflammation and immediate hypersensitivity. Curr Opin Immunol. 2021; 72: 94106, doi: 10.1016/j.coi.2021.04.001, indexed in Pubmed: 33932709.
  3. Wu R, Lyons JJ. Hereditary alpha-tryptasemia: a commonly inherited modifier of anaphylaxis. Curr Allergy Asthma Rep. 2021; 21(5): 33, doi: 10.1007/s11882-021-01010-1, indexed in Pubmed: 33970354.
  4. Lyons JJ, Yu X, Hughes JD, et al. Elevated basal serum tryptase identifies a multisystem disorder associated with increased TPSAB1 copy number. Nat Genet. 2016; 48(12): 15641569, doi: 10.1038/ng.3696, indexed in Pubmed: 27749843.
  5. Greiner G, Sprinzl B, Górska A, et al. Hereditary α tryptasemia is a valid genetic biomarker for severe mediator-related symptoms in mastocytosis. Blood. 2021; 137(2): 238247, doi: 10.1182/blood.2020006157, indexed in Pubmed: 32777817.
  6. Parente R, Giudice V, Cardamone C, et al. Secretory and membrane-associated biomarkers of mast cell activation and proliferation. Int J Mol Sci. 2023; 24(8): 7071, doi: 10.3390/ijms24087071, indexed in Pubmed: 37108232.
  7. Valent P, Hartmann K, Bonadonna P, et al. Mast cell activation syndromes: collegium internationale allergologicum update 2022. Int Arch Allergy Immunol. 2022; 183(7): 693705, doi: 10.1159/000524532, indexed in Pubmed: 35605594.
  8. Valent P, Akin C, Hartmann K, et al. Updated diagnostic criteria and classification of mast cell disorders: a consensus proposal. Hemasphere. 2021; 5(11): e646, doi: 10.1097/HS9.0000000000000646, indexed in Pubmed: 34901755.
  9. Valent P, Akin C, Sperr WR, et al. New insights into the pathogenesis of mastocytosis: emerging concepts in diagnosis and therapy. Annu Rev Pathol. 2023; 18: 361386, doi: 10.1146/annurev-pathmechdis-031521-042618, indexed in Pubmed: 36270293.
  10. Amin K. The role of mast cells in allergic inflammation. Respir Med. 2012; 106(1): 914, doi: 10.1016/j.rmed.2011.09.007, indexed in Pubmed: 22112783.
  11. Elieh Ali Komi D, Wöhrl S, Bielory L. Mast cell biology at molecular level: a comprehensive review. Clin Rev Allergy Immunol. 2020; 58(3): 342–365, doi: 10.1007/s12016-019-08769-2, indexed in Pubmed: 31828527.
  12. Caughey GH. Mast cell tryptases and chymases in inflammation and host defense. Immunol Rev. 2007; 217: 141154, doi: 10.1111/j.1600-065X.2007.00509.x, indexed in Pubmed: 17498057.
  13. Fujisawa D, Kashiwakura J, Kita H, et al. Expression of mas-related gene X2 on mast cells is upregulated in the skin of patients with severe chronic urticaria. J Allergy Clin Immun. 2014; 134(3): 622633.e9, doi: 10.1016/j.jaci.2014.05.004, indexed in Pubmed: 24954276.
  14. Foster B, Schwartz LB, Devouassoux G, et al. Characterization of mast-cell tryptase-expressing peripheral blood cells as basophils. J Allergy Clin Immunol. 2002; 109(2): 287293, doi: 10.1067/mai.2002.121454, indexed in Pubmed: 11842299.
  15. Katsoulis-Dimitriou K, Kotrba J, Voss M, et al. Mast cell functions linking innate sensing to adaptive immunity. Cells. 2020; 9(12): 2538, doi: 10.3390/cells9122538, indexed in Pubmed: 33255519.
  16. Picard M, Giavina-Bianchi P, Mezzano V. Expanding spectrum of mast cell activation disorders: monoclonal and idiopathic mast cell activation syndromes. Clin Ther. 2013; 35(5): 548562, doi: 10.1016/j.clinthera.2013.04.001, indexed in Pubmed: 23642289.
  17. Krystel-Whittemore M, Dileepan KN, Wood JG. Mast cell: a multi-functional master cell. Front Immunol. 2016; 6(6): 620, doi: 10.3389/fimmu.2015.00620, indexed in Pubmed: 26779180.
  18. Schwartz LB, Metcalfe DD, Miller JS, et al. Tryptase levels as an indicator of mast-cell activation in systemic anaphylaxis and mastocytosis. N Engl J Med. 1987; 316(26): 16221626, doi: 10.1056/NEJM198706253162603, indexed in Pubmed: 3295549.
  19. Theoharides TC, Valent P, Akin C, et al. Mast cells, mastocytosis, and related disorders. N Engl J Med. 2015; 373(2): 163172, doi: 10.1056/NEJMra1409760, indexed in Pubmed: 26154789.
  20. Lyons JJ. Hereditary alpha tryptasemia: genotyping and associated clinical features. Immunol Allergy Clin North Am. 2018; 38(3): 483495, doi: 10.1016/j.iac.2018.04.003, indexed in Pubmed: 30007465.
  21. Schwartz LB, Irani AM. Serum tryptase and the laboratory diagnosis of systemic mastocytosis. Hematol Oncol Clin North Am. 2000; 14(3): 641657, doi: 10.1016/s0889-8588(05)70300-2, indexed in Pubmed: 10909044.
  22. Glover SC, Carter MC, Korošec P, et al. Clinical relevance of inherited genetic differences in human tryptases: hereditary alpha-tryptasemia and beyond. Ann Allergy Asthma Immunol. 2021; 127(6): 638647, doi: 10.1016/j.anai.2021.08.009, indexed in Pubmed: 34400315.
  23. Trivedi NN, Tong Q, Raman K, et al. 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): 60726079, doi: 10.4049/jimmunol.179.9.6072, indexed in Pubmed: 17947681.
  24. Glover SC, Carlyle A, Lyons JJ. Hereditary alpha-tryptasemia despite normal tryptase-encoding gene copy number owing to copy number loss in trans. Ann Allergy Asthma Immunol. 2022; 128(4): 460461, doi: 10.1016/j.anai.2021.12.008, indexed in Pubmed: 34896311.
  25. Le QT, Lyons JJ, Naranjo AN, et al. Impact of naturally forming human α/β-tryptase heterotetramers in the pathogenesis of hereditary α-tryptasemia. J Exp Med. 2019; 216(10): 23482361, doi: 10.1084/jem.20190701, indexed in Pubmed: 31337736.
  26. Lyons JJ, Chovanec J, O’Connell MP, 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): 622632, doi: 10.1016/j.jaci.2020.06.035, indexed in Pubmed: 32717252.
  27. Carter MC, Maric I, Brittain EH, et al. A randomized double-blind, placebo-controlled study of omalizumab for idiopathic anaphylaxis. J Allergy Clin Immunol. 2021; 147(3): 10041010.e2, doi: 10.1016/j.jaci.2020.11.005, indexed in Pubmed: 33220353.
  28. Mendoza Alvarez LB, Barker R, Nelson C, et al. Clinical response to omalizumab in patients with hereditary α-tryptasemia. Ann Allergy Asthma Immunol. 2020; 124(1): 99100.e1, doi: 10.1016/j.anai.2019.09.026, indexed in Pubmed: 31605754.
  29. Romantowski J, Górska A, Lange M, et al. How to diagnose mast cell activation syndrome: practical considerations. Pol Arch Intern Med. 2020; 130(4): 317323, doi: 10.20452/pamw.15212, indexed in Pubmed: 32096778.
  30. Smiljkovic D, Kiss R, Lupinek C, et al. Microarray-based detection of allergen-reactive ige in patients with mastocytosis. J Allergy Clin Immunol Pract. 2020; 8(8): 27612768.e16, doi: 10.1016/j.jaip.2020.04.030, indexed in Pubmed: 32348913.
  31. Linden DR, Manning BP, Bunnett NW, et al. Agonists of proteinase-activated receptor 2 excite guinea pig ileal myenteric neurons. Eur J Pharmacol. 2001; 431(3): 311314, doi: 10.1016/s0014-2999(01)01447-9, indexed in Pubmed: 11730723.
  32. Schmidlin F, Amadesi S, Vidil R, et al. Expression and function of proteinase-activated receptor 2 in human bronchial smooth muscle. Am J Respir Crit Care Med. 2001; 164(7): 12761281, doi: 10.1164/ajrccm.164.7.2101157, indexed in Pubmed: 11673222.
  33. Dong X, Dong X. Peripheral and central mechanisms of itch. Neuron. 2018; 98(3): 482494, doi: 10.1016/j.neuron.2018.03.023, indexed in Pubmed: 29723501.
  34. Frateschi S, Camerer E, Crisante G, et al. PAR2 absence completely rescues inflammation and ichthyosis caused by altered CAP1/Prss8 expression in mouse skin. Nat Commun. 2011; 2: 161, doi: 10.1038/ncomms1162, indexed in Pubmed: 21245842.
  35. Steinhoff M, Neisius U, Ikoma A, et al. Proteinase-activated receptor-2 mediates itch: a novel pathway for pruritus in human skin. J Neurosci. 2003; 23(15): 61766180, doi: 10.1523/JNEUROSCI.23-15-06176.2003, indexed in Pubmed: 12867500.
  36. Vergnolle N, Bunnett NW, Sharkey KA, et al. Proteinase-activated receptor-2 and hyperalgesia: a novel pain pathway. Nat Med. 2001; 7(7): 821826, doi: 10.1038/89945, indexed in Pubmed: 11433347.
  37. Steinhoff M, Vergnolle N, Young SH. Agonists of proteinase-activated receptor 2 induce inflammation by a neurogenic mechanism. Nat Med. 2000; 6(2): 151158, doi: 10.1038/72247, indexed in Pubmed: 10655102.
  38. McNeil BD, Pundir P, Meeker S, et al. Identification of a mast-cell-specific receptor crucial for pseudo-allergic drug reactions. Nature. 2015; 519(7542): 237241, doi: 10.1038/nature14022, indexed in Pubmed: 25517090.
  39. Sabato V, Chovanec J, Faber M, et al. First identification of an inherited TPSAB1 quintuplication in a patient with clonal mast cell disease. J Clin Immunol. 2018; 38(4): 457459, doi: 10.1007/s10875-018-0506-y, indexed in Pubmed: 29748908.
  40. Sordi B, Vanderwert F, Crupi F, et al. Disease correlates and clinical relevance of hereditary α-tryptasemia in patients with systemic mastocytosis. J Allergy Clin Immunol. 2023; 151(2): 485493.e11, doi: 10.1016/j.jaci.2022.09.038, indexed in Pubmed: 36309122.
  41. Chantran Y. Biological diagnosis of hereditary alpha-tryptasemiaDiagnostic biologique de l’Alpha-Tryptasémie héréditaire. Rev. Fr. Allergol. 2023; 63(3): 103299.
  42. Sperr WR, Jordan JH, Fiegl M, 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(2): 136141, doi: 10.1159/000059404, indexed in Pubmed: 12065914.
  43. Valent P, Hartmann K, Bonadonna P, 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(8): 19411950, doi: 10.1016/j.jaip.2022.05.007, indexed in Pubmed: 35623575.
  44. Valent P, Akin C, Bonadonna P, et al. Proposed diagnostic algorithm for patients with suspected mast cell activation syndrome. J Allergy Clin Immunol Pract. 2019; 7(4): 11251133.e1, doi: 10.1016/j.jaip.2019.01.006, indexed in Pubmed: 30737190.
  45. Giannetti MP, Weller E, Bormans C, et al. Hereditary alpha-tryptasemia in 101 patients with mast cell activation-related symptomatology including anaphylaxis. Ann Allergy Asthma Immunol. 2021; 126(6): 655660, doi: 10.1016/j.anai.2021.01.016, indexed in Pubmed: 33465452.
  46. Valent P, Akin C, Gleixner KV, et al. Multidisciplinary challenges in mastocytosis and how to address with personalized medicine approaches. Int J Mol Sci. 2019; 20(12), doi: 10.3390/ijms20122976, indexed in Pubmed: 31216696.