Heritable risk for severe anaphylaxis associated with increased α-tryptase–encoding germline copy number at TPSAB1
Abstract
Background An elevated basal serum tryptase level is associated with severe systemic anaphylaxis, most notably caused by Hymenoptera envenomation. Although clonal mast cell disease is the culprit in some individuals, it does not fully explain this clinical association.Objective Our aim was to determine the prevalence and associated impact of tryptase genotypes on anaphylaxis in humans.Methods Cohorts with systemic mastocytosis (SM) and venom as well as idiopathic anaphylaxis from referral centers in Italy, Slovenia, and the United States, underwent tryptase genotyping by droplet digital PCR. Associated anaphylaxis severity (Mueller scale) was subsequently examined. Healthy volunteers and controls with nonatopic disease were recruited and tryptase was genotyped by droplet digital PCR and in silico analysis of genome sequence, respectively. The effects of pooled and recombinant human tryptases, protease activated receptor 2 agonist and antagonist peptides, and a tryptase-neutralizing mAb on human umbilical vein endothelial cell permeability were assayed using a Transwell system.Results Hereditary α-tryptasemia (HαT)-a genetic trait caused by increased α-tryptase-encoding Tryptase-α/β1 (TPSAB1) copy number resulting in elevated BST level-was common in healthy individuals (5.6% [n = 7 of 125]) and controls with nonatopic disease (5.3% [n = 21 of 398]). HαT was associated with grade IV venom anaphylaxis (relative risk = 2.0; P < .05) and more prevalent in both idiopathic anaphylaxis (n = 8 of 47; [17%; P = .006]) and SM (n = 10 of 82 [12.2%; P = .03]) relative to the controls. Among patients with SM, concomitant HαT was associated with increased risk for systemic anaphylaxis (relative risk = 9.5; P = .007). In vitro, protease-activated receptor-2-dependent vascular permeability was induced by pooled mature tryptases but not α- or β-tryptase homotetramers.Conclusions Risk for severe anaphylaxis in humans is associated with inherited differences in α-tryptase-encoding copies at TPSAB1.
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Hereditary alpha-tryptasemia may be associated with an increased severity of anaphylactic reactions and other mediator-induced symptoms in patients with mastocytosis and venom allergy.
“Further, H a T may be associated with an increased severity of anaphylactic reactions and other mediator-induced symptoms in patients with mastocytosis and venom allergy. 25,129”
From Selecting the Right Criteria and Proper Classification to Diagnose Mast Cell Activation Syndromes: A Critical Review (2021) · cites this paper as [129]
The prevalence of HαT in patients with SM can reach up to 12%-20%.
“in patients with SM, where it can reach up to 12%–20% (17, 19, 22, 23).”
From Defining “Normal” basal serum tryptase levels: a context-dependent approach to improve diagnostics in systemic mastocytosis (2025) · cites this paper as [17]
Severe episodes were twice more frequent in individuals with both SM and HαT than in those with SM but without HαT.
“severe episodes were twice more frequent in individuals with both SM and HαT than in those with SM but without HαT (17, 18).”
From Defining “Normal” basal serum tryptase levels: a context-dependent approach to improve diagnostics in systemic mastocytosis (2025) · cites this paper as [17]
There is a consensus that HαT is a risk modifier of severe anaphylaxis.
“There is a consensus that HαT is a risk modifier of severe anaphylaxis [21,48,49,50,51,52,53].”
From Diagnostic Significance of Tryptase for Suspected Mast Cell Disorders (2023) · cites this paper as [48]
Alpha/beta-tryptase heterotetrameric tryptases have expanded biologic functions relative to mature beta-tryptases and may offer a possible mechanism explaining mast cell activation in individuals with hereditary alpha-tryptasemia.
“A recent description of a / b -tryptase heterotetrameric tryptases, which have expanded biologic functions relative to mature b -tryptases, may offer a possible mechanism explaining MCA in these individuals. 128,129”
From Selecting the Right Criteria and Proper Classification to Diagnose Mast Cell Activation Syndromes: A Critical Review (2021) · cites this paper as [129]
An approximately two to three times higher prevalence of hereditary alpha-tryptasemia has been reported in two large cohorts of systemic mastocytosis patients, and hereditary alpha-tryptasemia concurrently occurring with MCAS has been reported.
“However, an approximately two to three times higher prevalence of H a T has been reported in two large cohorts of SM patients 25,129 ; also, H a T concurrently occurring with MCAS has been reported. 130,131”
From Selecting the Right Criteria and Proper Classification to Diagnose Mast Cell Activation Syndromes: A Critical Review (2021) · cites this paper as [129]
HαT is enriched in patients with SM, Hymenoptera-allergic patients with severe anaphylaxis, and patients with idiopathic anaphylaxis.
“HαT is enriched in patients with SM,42,43 in Hymenoptera-allergic patients with severe anaphylaxis,44,45 and in patients with idiopathic anaphylaxis.42,43,45,46”
From Mast cell activation syndrome: Current understanding and research needs (2024) · cites this paper as [45]
HaT has been shown to be an independent heritable genetic risk factor of severe anaphylaxis.
“because HaT has been shown to be an independent heritable genetic risk factor of severe anaphylaxis.23”
From Low Prevalence of Idiopathic Mast Cell Activation Syndrome Among 703 Patients With Suspected Mast Cell Disorders (2024) · cites this paper as [23]
Cites
Activation of Endothelial Cell Protease Activated Receptor 1 by the Protein C Pathway
Riewald, M., Petrovan, R. J., Donner, A. J., Mueller, B. M., & Ruf, W. (2002) · Science · doi:10.1126/science.1071699 · Cited by 832 · see citing works
Mastocytosis: 2016 updated WHO classification and novel emerging treatment concepts
Valent, P., Akin, C., & Metcalfe, D. D. (2016) · Blood · doi:10.1182/blood-2016-09-731893 · Cited by 680 · see citing works
Self-citationBrockow, K., Jofer, C., Behrendt, H., & Ring, J. (2008) · Allergy · doi:10.1111/j.1398-9995.2007.01569.x · Cited by 523 · see citing works
Diagnostic Value of Tryptase in Anaphylaxis and Mastocytosis
Schwartz, L. B. (2006) · Immunology and Allergy Clinics of North America · doi:10.1016/j.iac.2006.05.010 · Cited by 477 · see citing works
Self-citationRuëff, F., Bernhard Przybilla, A., Bilò, M. B., Müller, U., Scheipl, F., Aberer, W., Birnbaum, J., Bodzenta‐Łukaszyk, A., Bonifazi, F., Bucher, C., et al. (2009) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2009.08.027 · Cited by 429 · see citing works
Diagnosis and Treatment of Insect Sensitivity
Mueller, H. L. (1966) · Journal of Asthma Research · doi:10.3109/02770906609106941 · Cited by 425 · see citing works
Lyons, J. J., Yu, X., Hughes, J. D., Le, Q. T., Jamil, A., Bai, Y., Ho, N., Zhao, M., Liu, Y., O'Connell, M. P., et al. (2016) · Nature Genetics · doi:10.1038/ng.3696 · Cited by 394 · see citing works
Self-citationMast Cell Tryptase Controls Paracellular Permeability of the Intestine
Jacob, C., Yang, P.-C., Darmoul, D., Amadesi, S., Saito, T., Cottrell, G. S., Coelho, A.-M., Singh, P., Grady, E. F., Perdue, M., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m506338200 · Cited by 334 · see citing works
Epidemiology of systemic mastocytosis in Denmark
Cohen, S. S., Skovbo, S., Vestergaard, H., Kristensen, T. K., Møller, M. B., Bindslev‐Jensen, C., Fryzek, J. P., & Broesby‐Olsen, S. (2014) · British Journal of Haematology · doi:10.1111/bjh.12916 · Cited by 235 · see citing works
Haeberli, G., Brönnimann, M. P., Hunziker, T., & Müller, U. (2003) · Clinical & Experimental Allergy · doi:10.1046/j.1365-2222.2003.01755.x · Cited by 218 · see citing works
The fibrinogenolytic activity of purified tryptase from human lung mast cells.
Schwartz, L. B., Bradford, T. R., Littman, B. H., & Wintroub, B. U. (1985) · The Journal of Immunology · doi:10.4049/jimmunol.135.4.2762 · Cited by 195 · see citing works
Self-citationDiagnosis and treatment of insect sensitivity
Müller, H. M. (1966) · Medical Entomology and Zoology · Cited by 192 · see citing works
Generation of C3a anaphylatoxin from human C3 by human mast cell tryptase.
Schwartz, L. B., Kawahara, M. S., Hugli, T. E., Vik, D., Fearon, D. T., & Austen, K. F. (1983) · The Journal of Immunology · doi:10.4049/jimmunol.130.4.1891 · Cited by 184 · see citing works
Self-citationLyons, J. J. (2018) · Immunology and Allergy Clinics of North America · doi:10.1016/j.iac.2018.04.003 · Cited by 179 · see citing works
Self-citationHigh prevalence of anaphylaxis in patients with systemic mastocytosis - a single-centre experience
Gülen, T., Hägglund, H., Dahlén, B., & Nilsson, G. (2014) · Clinical & Experimental Allergy · doi:10.1111/cea.12225 · Cited by 156 · see citing works
Tryptase genetics and anaphylaxis
Caughey, G. H. (2006) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2006.02.026 · Cited by 150 · see citing works
Lyons, J. J., Sun, G., Stone, K. D., Nelson, C., Wisch, L., O'Brien, M., Jones, N., Lindsley, A., Komarow, H. D., Bai, Y., et al. (2014) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2013.11.039 · Cited by 136 · see citing works
Self-citationSensitive KIT D816V mutation analysis of blood as a diagnostic test in mastocytosis
Kristensen, T. K., Vestergaard, H., Bindslev‐Jensen, C., Møller, M. B., & Broesby‐Olsen, S. (2014) · American Journal of Hematology · doi:10.1002/ajh.23672 · Cited by 126 · see citing works
Le, Q. T., Lyons, J. J., Naranjo, A. N., Olivera, A., Lazarus, R. A., Metcalfe, D. D., Milner, J. D., & Schwartz, L. B. (2019) · Journal of Experimental Medicine · doi:10.1084/jem.20190701 · Cited by 126 · see citing works
Self-citationSchwartz, L. B., Min, H.-K., Ren, S., Xia, H.-Z., Hu, J., Zhao, W., Moxley, G., & Fukuoka, Y. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.170.11.5667 · Cited by 120 · see citing works
Self-citationJara-Acevedo, M., Teodosio, C., Sanchez-Muñoz, L., Álvarez-Twose, I., Mayado, A., Caldas, C., Matito, A., Morgado, J. M., Muñoz-González, J. I., Escribano, L., et al. (2015) · Modern Pathology · doi:10.1038/modpathol.2015.72 · Cited by 114 · see citing works
An Allosteric Anti-tryptase Antibody for the Treatment of Mast Cell-Mediated Severe Asthma
Maun, H. R., Jackman, J. K., Choy, D. F., Loyet, K. M., Staton, T. L., Jia, G., Dressen, A., Hackney, J. A., Bremer, M. C. D., Walters, B. T., et al. (2019) · Cell · doi:10.1016/j.cell.2019.09.009 · Cited by 112 · see citing works
Self-citationDengue virus–elicited tryptase induces endothelial permeability and shock
Rathore, A. P. S., Mantri, C. K., Aman, S. A. B., Syenina, A., Ooi, J. S. G., Jagaraj, C. J., Goh, C. C., Tissera, H. A., Wilder‐Smith, A., Ng, L. G., et al. (2019) · Journal of Clinical Investigation · doi:10.1172/jci128426 · Cited by 94 · see citing works
[6] Tryptase: A mast cell serine protease
Schwartz, L. B. (1994) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(94)44008-5 · Cited by 89 · see citing works
Self-citationClinical characteristics and risk profile of patients with elevated baseline serum tryptase
Fellinger, C., Hemmer, W., Wöhrl, S., Sesztak‐Greinecker, G., Jarisch, R., & Wantke, F. (2014) · Allergologia et Immunopathologia · doi:10.1016/j.aller.2014.05.002 · Cited by 89 · see citing works
Huang, C. B., Li, L., Krilis, S. A., Chanasyk, K., Tang, Y., Li, Z., Hunt, J. E., & Stevens, R. L. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.28.19670 · Cited by 87 · see citing works
Digital PCR: A Sensitive and Precise Method for KIT D816V Quantification in Mastocytosis
Greiner, G., Gurbisz, M., Ratzinger, F., Witzeneder, N., Simonitsch-Klupp, I., Mitterbauer-Hohendanner, G., Mayerhofer, M., Müllauer, L., Sperr, W. R., Valent, P., et al. (2018) · Clinical Chemistry · doi:10.1373/clinchem.2017.277897 · Cited by 83 · see citing works
Basal serum tryptase level correlates with severity of hymenoptera sting and age.
Kucharewicz, I., Bodzenta‐Łukaszyk, A., Szymanski, W., Mroczko, B., & Szmitkowski, M. (2007) · PubMed · Cited by 75 · see citing works
Sabato, V., Chovanec, J., Faber, M., Milner, J. D., Ebo, D., & Lyons, J. J. (2018) · Journal of Clinical Immunology · doi:10.1007/s10875-018-0506-y · Cited by 73 · see citing works
Self-citationŞahiner, Ü. M., Yavuz, S. T., Büyüktiryaki, B., Cavkaytar, Ö., Yılmaz, E. A., Tuncer, A., & Saçkesen, C. (2013) · Allergy · doi:10.1111/all.12317 · Cited by 72 · see citing works
Hox, V., O'Connell, M. P., Lyons, J. J., Sackstein, P., Dimaggio, T., Jones, N., Nelson, C., Boehm, M., Holland, S. M., Freeman, A. F., et al. (2016) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2015.11.024 · Cited by 64 · see citing works
Self-citationSerum Baseline Tryptase Level as a Marker for the Severity of Anaphylaxis
Aniceto, V., Dias, M. M., Melo, J. M. L., Neto, O. T., Aragon, D. C., Maia, L. S. M., Moreno, A. S., & Arruda, L. K. (2019) · International Archives of Allergy and Immunology · doi:10.1159/000497235 · Cited by 35 · see citing works
Disease spectrum in patients with elevated serum tryptase levels
Aberer, E., SAVIC, S. L., Bretterklieber, A., Reiter, H., Berghold, A., & Aberer, W. (2014) · Australasian Journal of Dermatology · doi:10.1111/ajd.12146 · Cited by 22 · see citing works
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EAACI guidelines: Anaphylaxis (2021 update)
Muraro, A. M., Worm, M., Alviani, C., Cardona, V., DunnGalvin, A., Garvey, L. H., Riggioni, C., de Silva, D., Angier, E., Arasi, S., et al. (2021) · Allergy · doi:10.1111/all.15032 · Cited by 637 · see citing works
Anaphylaxis: A 2023 practice parameter update
Golden, D. B. K., Wang, J., Waserman, S., Akin, C., Campbell, R. L., Ellis, A. K., Greenhawt, M., Lang, D. M., Ledford, D. K., Lieberman, P., et al. (2023) · Annals of Allergy Asthma & Immunology · doi:10.1016/j.anai.2023.09.015 · Cited by 383 · see citing works
Updated Diagnostic Criteria and Classification of Mast Cell Disorders: A Consensus Proposal
Valent, P., Akin, C., Hartmann, K., Alvarez-Twose, I., Brockow, K., Hermine, O., Niedoszytko, M., Schwaab, J., Lyons, J. J., Carter, M. C., et al. (2021) · HemaSphere · doi:10.1097/hs9.0000000000000646 · Cited by 317 · see citing works
Self-citationGreiner, G., Sprinzl, B., Górska, A., Ratzinger, F., Gurbisz, M., Witzeneder, N., Schmetterer, K. G., Gisslinger, B., Uyanik, G., Hadzijusufovic, E., et al. (2021) · Blood · doi:10.1182/blood.2020006157 · Cited by 189 · see citing works
The ingenious mast cell: Contemporary insights into mast cell behavior and function
Dahlin, J. S., Maurer, M., Metcalfe, D. D., Pejler, G., Sagi‐Eisenberg, R., & Nilsson, G. P. (2021) · Allergy · doi:10.1111/all.14881 · Cited by 154 · see citing works
Self-citationPotential mechanisms of anaphylaxis to COVID-19 mRNA vaccines
Risma, K., Edwards, K. M., Hummell, D. S., Little, F. F., Norton, A. E., Stallings, A. P., Wood, R. A., & Milner, J. D. (2021) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2021.04.002 · Cited by 152 · see citing works
Self-citationRisk factors for severe reactions in food allergy: Rapid evidence review with meta‐analysis
Turner, P., Arasi, S., Ballmer-Weber, B. K., Conrado, A. B., Deschildre, A., Gerdts, J. D., Halken, S., Muraro, A. M., Patel, N., van Ree, R., et al. (2022) · Allergy · doi:10.1111/all.15318 · Cited by 147 · see citing works
Systemic mastocytosis in adults: 2023 update on diagnosis, risk stratification and management
Pardanani, A. (2023) · American Journal of Hematology · doi:10.1002/ajh.26962 · Cited by 132 · see citing works
Valent, P., Akin, C., Nedoszytko, B., Bonadonna, P., Hartmann, K., Niedoszytko, M., Brockow, K., Siebenhaar, F., Triggiani, M., Arock, M., et al. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21239030 · Cited by 92 · see citing works
Self-citationHereditary alpha tryptasemia is not associated with specific clinical phenotypes
Chollet, M. B., & Akin, C. (2022) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2021.06.017 · Cited by 90 · see citing works
Valent, P., Hartmann, K., Bonadonna, P., Gülen, T., Brockow, K., Alvarez-Twose, I., Hermine, O., Niedoszytko, M., Carter, M. C., Hoermann, G., et al. (2022) · The Journal of Allergy and Clinical Immunology: In Practice · doi:10.1016/j.jaip.2022.05.007 · Cited by 90 · see citing works
Self-citationCOVID-19 vaccines adverse events: potential molecular mechanisms
Lamprinou, M., Sachinidis, A., Stamoula, Ε., Vavilis, T., & Papazisis, G. (2023) · Immunologic Research · doi:10.1007/s12026-023-09357-5 · Cited by 89 · see citing works
Defining baseline variability of serum tryptase levels improves accuracy in identifying anaphylaxis
Mateja, A., Wang, Q., Chovanec, J., Kim, J., Wilson, K. J., Schwartz, L. B., Glover, S. C., Carter, M. C., Metcalfe, D. D., Brittain, E., et al. (2022) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2021.08.007 · Cited by 91 · see citing works
Self-citationNew Insights into the Pathogenesis of Mastocytosis: Emerging Concepts in Diagnosis and Therapy
Valent, P., Akin, C., Sperr, W. R., Horny, H., Arock, M., Metcalfe, D. D., & Galli, S. J. (2022) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathmechdis-031521-042618 · Cited by 87 · see citing works
Self-citationGiannetti, M. P., Weller, E., Bormans, C., Novak, P., Hamilton, M. J., & Castells, M. (2021) · Annals of Allergy, Asthma & Immunology · doi:10.1016/j.anai.2021.01.016 · Cited by 84 · see citing works
Gülen, T., Akin, C., Bonadonna, P., Siebenhaar, F., Broesby-Olsen, S., Brockow, K., Niedoszytko, M., Nedoszytko, B., Oude Elberink, H. N. G., Butterfield, J. H., et al. (2021) · The Journal of Allergy and Clinical Immunology: In Practice · doi:10.1016/j.jaip.2021.06.011 · Cited by 83 · see citing works
“Further, HaT may be associated with an increased severity of anaphylactic reactions and other mediator-induced symptoms in patients with mastocytosis and venom allergy.(25,129) The exact percentage of patients with clonal and idiopathic MCAS who concurrently have HaT is unknown.”
BackgroundSelf-citationVitte, J., Sabato, V., Tacquard, C., Garvey, L. H., Michel, M., Mertes, P.-M., Ebo, D. G., Schwartz, L. B., & Castells, M. C. (2021) · The Journal of Allergy and Clinical Immunology In Practice · doi:10.1016/j.jaip.2021.03.011 · Cited by 79 · see citing works
Self-citationValent, P., Hartmann, K., Schwaab, J., Alvarez-Twose, I., Brockow, K., Bonadonna, P., Hermine, O., Niedoszytko, M., Carter, M. C., Hoermann, G., et al. (2022) · The Journal of Allergy and Clinical Immunology: In Practice · doi:10.1016/j.jaip.2022.03.007 · Cited by 72 · see citing works
Self-citationDiagnosis and treatment of Hymenoptera venom allergy
Ruëff, F., Bauer, A., Becker, S., Brehler, R., Brockow, K., Chaker, A. M., Darsow, U. G., Fischer, J., Fuchs, T., Gerstlauer, M., et al. (2023) · Allergologie select · doi:10.5414/alx02430e · Cited by 72 · see citing works
The Genetic Basis and Clinical Impact of Hereditary Alpha-Tryptasemia
Luskin, K. T., White, A. A., & Lyons, J. J. (2021) · The Journal of Allergy and Clinical Immunology In Practice · doi:10.1016/j.jaip.2021.03.005 · Cited by 67 · see citing works
Self-citationŠelb, J., Rijavec, M., Eržen, R., Zidarn, M., Kopač, P., Škerget, M., Bajrović, N., Luzar, A. D., Park, Y. H., Liu, Y., et al. (2021) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2021.02.043 · Cited by 65 · see citing works
Self-citationThe international consensus classification of mastocytosis and related entities
Leguit, R. J., Wang, S. A., George, T. I., Tzankov, A., & Orazi, A. (2023) · Virchows Archiv · doi:10.1007/s00428-022-03423-3 · Cited by 65 · see citing works
Clinical relevance of inherited genetic differences in human tryptases
Glover, S. C., Carter, M. C., Korošec, P., Bonadonna, P., Schwartz, L. B., Milner, J. D., Caughey, G. H., Metcalfe, D. D., & Lyons, J. J. (2021) · Annals of Allergy, Asthma & Immunology · doi:10.1016/j.anai.2021.08.009 · Cited by 64 · see citing works
Self-citationMast cells in food allergy: Inducing immediate reactions and shaping long-term immunity
Oettgen, H. C. (2022) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2022.10.003 · Cited by 60 · see citing works
Chovanec, J., Tunc, I., Hughes, J., Halstead, J., Mateja, A., Liu, Y., O’Connell, M. P., Kim, J., Park, Y. H., Wang, Q., et al. (2023) · Blood Advances · doi:10.1182/bloodadvances.2022007936 · Cited by 62 · see citing works
Self-citationMast cell activation syndromes: Collegium Internationale Allergologicum update 2022
Valent, P., Hartmann, K., Bonadonna, P., Niedoszytko, M., Triggiani, M., Arock, M., & Brockow, K. (2022) · International Archives of Allergy and Immunology · doi:10.1159/000524532 · Cited by 55 · see citing works
Self-citationHymenoptera venom-induced anaphylaxis and hereditary alpha-tryptasemia
O’Connell, M. P., & Lyons, J. J. (2020) · Current Opinion in Allergy & Clinical Immunology · doi:10.1097/aci.0000000000000678 · Cited by 53 · see citing works
Self-citationInherited and acquired determinants of serum tryptase levels in humans
Lyons, J. J. (2021) · Annals of Allergy, Asthma & Immunology · doi:10.1016/j.anai.2021.06.019 · Cited by 52 · see citing works
Self-citationSordi, B., Vanderwert, F., Crupi, F., Gesullo, F., Zanotti, R., Bonadonna, P., Crosera, L., Elena, C., Fiorelli, N., Ferrari, J., et al. (2023) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2022.09.038 · Cited by 51 · see citing works
Self-citationAnaphylaxis and Mast Cell Disorders
Gülen, T., & Akin, C. (2022) · Immunology and Allergy Clinics of North America · doi:10.1016/j.iac.2021.09.007 · Cited by 51 · see citing works
Sprinzl, B., Greiner, G., Uyanik, G., Arock, M., Haferlach, T., Sperr, W. R., Valent, P., & Hoermann, G. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22052458 · Cited by 51 · see citing works
Mast cell tryptases in allergic inflammation and immediate hypersensitivity
Lyons, J. J., & Yi, T. (2021) · Current Opinion in Immunology · doi:10.1016/j.coi.2021.04.001 · Cited by 54 · see citing works
Self-citationIncorporating Tryptase Genotyping Into the Workup and Diagnosis of Mast Cell Diseases and Reactions
Lyons, J. J., Greiner, G., Hoermann, G., & Metcalfe, D. D. (2022) · The Journal of Allergy and Clinical Immunology In Practice · doi:10.1016/j.jaip.2022.05.003 · Cited by 48 · see citing works
Self-citationMediator-Related Symptoms and Anaphylaxis in Children with Mastocytosis
Brockow, K., Plata‐Nazar, K., Lange, M., Nedoszytko, B., Niedoszytko, M., & Valent, P. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22052684 · Cited by 48 · see citing works
Elevated Basal Serum Tryptase: Disease Distribution and Variability in a Regional Health System
Waters, A. M., Park, H. J., Weskamp, A. L., Mateja, A., Kachur, M. E., Lyons, J. J., Rosen, B. J., & Boggs, N. A. (2022) · The Journal of Allergy and Clinical Immunology In Practice · doi:10.1016/j.jaip.2021.12.031 · Cited by 46 · see citing works
Self-citationMast cell activation syndrome: Current understanding and research needs
Castells, M., Giannetti, M. P., Hamilton, M. J., Novak, P., Pozdnyakova, O., Nicoloro-SantaBarbara, J., Jennings, S. V., Francomano, C., Kim, B., Glover, S. C., et al. (2024) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2024.05.025 · Cited by 45 · see citing works
Self-citationHamilton, M. J., Zhao, M., Giannetti, M. P., Weller, E., Hufdhi, R., Novak, P., Mendoza-Alvarez, L. B., Hornick, J., Lyons, J. J., Glover, S. C., et al. (2021) · American Journal of Surgical Pathology · doi:10.1097/pas.0000000000001676 · Cited by 44 · see citing works
Self-citationPathophysiological, Cellular, and Molecular Events of the Vascular System in Anaphylaxis
Nuñez‐Borque, E., Fernández‐Bravo, S., Yuste‐Montalvo, A., & Esteban, V. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.836222 · Cited by 47 · see citing works
Giannetti, M. P., Akin, C., Hufdhi, R., Hamilton, M. J., Weller, E., van Anrooij, B., Lyons, J. J., Hornick, J. L., Pinkus, G., Castells, M., et al. (2021) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2020.11.017 · Cited by 43 · see citing works
Self-citationHereditary alpha-tryptasemia: a commonly inherited modifier of anaphylaxis
Wu, R., & Lyons, J. J. (2021) · Current Allergy and Asthma Reports · doi:10.1007/s11882-021-01010-1 · Cited by 43 · see citing works
Self-citationArock, M., Hoermann, G., Sotlar, K., Hermine, O., Sperr, W. R., Hartmann, K., Brockow, K., Akin, C., Triggiani, M., Broesby‐Olsen, S., et al. (2022) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2022.04.004 · Cited by 42 · see citing works
Self-citationAnaphylaxis knowledge gaps and future research priorities: A consensus report
Dribin, T. E., Schnadower, D., Wang, J., Camargo, C. A., Michelson, K. A., Shaker, M. S., Rudders, S. A., Vyles, D. E., Golden, D. B. K., Spergel, J. M., et al. (2021) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2021.07.035 · Cited by 41 · see citing works
González‐de‐Olano, D., Navarro‐Navarro, P., Muñoz‐González, J. I., Sánchez‐Muñoz, L., Henriques, A., de‐Andrés‐Martín, A., Peralta‐Arjonilla, D., Mayado, A., Jara‐Acevedo, M., García‐Montero, A. C., et al. (2024) · Allergy · doi:10.1111/all.15911 · Cited by 38 · see citing works
Valent, P., Hartmann, K., Hoermann, G., Reiter, A., Álvarez‐Twöse, I., Brockow, K., Bonadonna, P., Hermine, O., Niedoszytko, M., Carter, M. C., et al. (2024) · The Journal of Allergy and Clinical Immunology In Practice · doi:10.1016/j.jaip.2024.08.044 · Cited by 40 · see citing works
Self-citationClonal mast cell disorders and hereditary α-tryptasemia as risk factors for anaphylaxis
Kačar, M., Rijavec, M., Šelb, J., & Korošec, P. (2023) · Clinical & Experimental Allergy · doi:10.1111/cea.14264 · Cited by 37 · see citing works
Self-citationPolivka, L., Madrange, M., Livideanu, C. B., Barète, S., Ballul, T., Neuraz, A., Greco, C., Agopian, J., Brenet, F. A., Dubreuil, P. C., et al. (2023) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2023.08.015 · Cited by 37 · see citing works
Korošec, P., Sturm, G. J., Lyons, J. J., Marolt, T. P., Svetina, M., Košnik, M., Zidarn, M., Kačar, M., Frelih, N., Lalek, N., et al. (2024) · Allergy · doi:10.1111/all.16084 · Cited by 40 · see citing works
Self-citationClinical Impact of Inherited and Acquired Genetic Variants in Mastocytosis
Nedoszytko, B., Arock, M., Lyons, J. J., Bachelot, G., Schwartz, L. B., Reiter, A., Jawhar, M., Schwaab, J., Lange, M., Greiner, G., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22010411 · Cited by 37 · see citing works
Self-citationResponse Criteria in Advanced Systemic Mastocytosis: Evolution in the Era of KIT Inhibitors
Shomali, W. E., & Gotlib, J. R. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22062983 · Cited by 37 · see citing works
World Health Organization Classification and Diagnosis of Mastocytosis
Valent, P., Sotlar, K., Horny, H., Arock, M., & Akin, C. (2023) · Immunology and Allergy Clinics of North America · doi:10.1016/j.iac.2023.04.011 · Cited by 36 · see citing works
The Role of Mast Cells in the Induction and Maintenance of Inflammation in Selected Skin Diseases
Woźniak, E., Owczarczyk-Saczonek, A. B., Lange, M., Czarny, J. H., Wygonowska, E., Placek, W. J., & Nedoszytko, B. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24087021 · Cited by 35 · see citing works
Idiopathic Anaphylaxis: a Perplexing Diagnostic Challenge for Allergists
Gülen, T., & Akin, C. (2021) · Current Allergy and Asthma Reports · doi:10.1007/s11882-021-00988-y · Cited by 35 · see citing works
Severe food allergy reactions are associated with α-tryptase
Lang, A., Kubala, S., Grieco, M. C., Mateja, A., Pongracic, J., Liu, Y., Frischmeyer-Guerrerio, P. A., Kumar, R., & Lyons, J. J. (2023) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2023.07.014 · Cited by 36 · see citing works
Management of Refractory Anaphylaxis: An Overview of Current Guidelines
Pouessel, G., Dribin, T. E., Tacquard, C. A., Tanno, L. K., Cardona, V., Worm, M., Deschildre, A., Muraro, A. M., Garvey, L. H., & Turner, P. (2024) · Clinical & Experimental Allergy · doi:10.1111/cea.14514 · Cited by 33 · see citing works
Prevalence of mastocytosis and Hymenoptera venom allergy in the United States
Schuler, C. F., IV, Volertas, S., Khokhar, D. S., Yüce, H., Chen, L., Başer, O., Montejo, J. M., & Akin, C. (2021) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2021.04.013 · Cited by 33 · see citing works
Kopač, P., Čustović, A., Zidarn, M., Šilar, M., Šelb, J., Bajrović, N., Eržen, R., Košnik, M., & Korošec, P. (2021) · The Journal of Allergy and Clinical Immunology In Practice · doi:10.1016/j.jaip.2021.04.045 · Cited by 33 · see citing works
Self-citationMast cell disorders are associated with decreased cerebral blood flow and small fiber neuropathy
Novak, P., Giannetti, M. P., Weller, E., Hamilton, M. J., & Castells, M. (2022) · Annals of Allergy, Asthma & Immunology · doi:10.1016/j.anai.2021.10.006 · Cited by 32 · see citing works
Tryptase in type I hypersensitivity
Michel, M., Klingebiel, C., & Vitte, J. (2022) · Annals of Allergy Asthma & Immunology · doi:10.1016/j.anai.2022.08.996 · Cited by 31 · see citing works
Konnikova, L., Robinson, T. O., Owings, A. H., Shirley, J. F., Davis, E. M., Tang, Y., Wall, S. M., Li, J., Hasan, M., Gharaibeh, R. Z., et al. (2021) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2021.04.004 · Cited by 30 · see citing works
Self-citationReview and updates on systemic mastocytosis and related entities
Li, J. Y., Ryder, C. B., Zhang, H., Cockey, S. G., Hyjek, E., Moscinski, L. C., Sagatys, E., & Song, J. (2023) · Cancers · doi:10.3390/cancers15235626 · Cited by 31 · see citing works
Vega, A., Jiménez‐Rodriguez, T. W., Barranco, R., Bartra, J., Diéguez, M., Doña, I., Fernández‐Rivas, M., Gandolfo-Cano, M., Lasarte, G. G., Gonzalez-Mancebo, E., et al. (2021) · Journal of Investigational Allergology and Clinical Immunology · doi:10.18176/jiaci.0712 · Cited by 29 · see citing works
Akin, C., Arock, M., Carter, M. C., George, T. I., & Valent, P. (2025) · Nature Reviews Disease Primers · doi:10.1038/s41572-025-00611-8 · Cited by 28 · see citing works
Self-citationEbo, D. G., De Puysseleyr, L. P., Van Gasse, A. L., Elst, J., Poorten, M.-L. V. D., Faber, M. A., Mertens, C., Van Houdt, M., Hagendorens, M. M., Sermeus, L., et al. (2021) · The Journal of Allergy and Clinical Immunology In Practice · doi:10.1016/j.jaip.2021.03.050 · Cited by 26 · see citing works
Self-citationDifferential mast cell mediators in systemic mastocytosis and hereditary α-tryptasemia
Giannetti, M. P., Godwin, G., Weller, E., Butterfield, J. H., & Castells, M. (2022) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2022.04.025 · Cited by 25 · see citing works
(2023) · The Journal of Allergy and Clinical Immunology: In Practice · doi:10.1016/j.jaip.2023.07.001 · Cited by 25 · see citing works
Self-citationPouessel, G., Tacquard, C. A., Tanno, L. K., Mertès, P., & Lezmi, G. (2024) · Clinical & Experimental Allergy · doi:10.1111/cea.14434 · Cited by 25 · see citing works
Targeting Mast Cells with Biologics
Lyons, J. J., & Metcalfe, D. D. (2020) · Immunology and Allergy Clinics of North America · doi:10.1016/j.iac.2020.06.007 · Cited by 27 · see citing works
Self-citationAlpha-tryptase as a risk-modifying factor for mast cell–mediated reactions
Shin, H., & Lyons, J. J. (2024) · Current Allergy and Asthma Reports · doi:10.1007/s11882-024-01136-y · Cited by 24 · see citing works
Self-citationBone Marrow Mastocytosis: A Diagnostic Challenge
Zanotti, R., Tanasi, I., Bernardelli, A., Orsolini, G., & Bonadonna, P. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10071420 · Cited by 24 · see citing works
Self-citationZaghmout, T., Maclachlan, L., Bedi, N., & Gülen, T. (2024) · The Journal of Allergy and Clinical Immunology: In Practice · doi:10.1016/j.jaip.2023.11.041 · Cited by 23 · see citing works
Gotlib, J. R., Schwaab, J., Shomali, W. E., George, T. I., Radia, D. H., Castells, M., Carter, M. C., Hartmann, K., Álvarez‐Twöse, I., Brockow, K., et al. (2022) · The Journal of Allergy and Clinical Immunology In Practice · doi:10.1016/j.jaip.2022.05.034 · Cited by 23 · see citing works
Self-citationRecent insights into the mechanisms of anaphylaxis
Stevens, W. W., Kraft, M., & Eisenbarth, S. C. (2023) · Current Opinion in Immunology · doi:10.1016/j.coi.2023.102288 · Cited by 23 · see citing works
Updates and Recent Advances on Venom Immunotherapy
Floyd, M. L., Adams, K. E., & Golden, D. B. K. (2023) · Current Treatment Options in Allergy · doi:10.1007/s40521-023-00336-7 · Cited by 23 · see citing works
Niedoszytko, M., Górska, A., Brockow, K., Bonadonna, P., Lange, M., Kluin‐Nelemans, H. C., Oude‐Elberink, H., Sabato, V., Shoumariyeh, K., von Bubnoff, D., et al. (2024) · Allergy · doi:10.1111/all.16132 · Cited by 23 · see citing works
Self-citationA Puzzling Mast Cell Trilogy: Anaphylaxis, MCAS, and Mastocytosis
Gülen, T. (2023) · Diagnostics · doi:10.3390/diagnostics13213307 · Cited by 21 · see citing works
Assessment of Osteoporosis and Fracture Risk in Mastocytosis within a North American Cohort
Makovoz, A., Wang, J., Oshegbo, G., Park, Y. H., Lyons, J. J., Eisch, A. R., Scott, L. M., Reynolds, J. C., Ortega‐Villa, A. M., Metcalfe, D. D., et al. (2021) · The Journal of Allergy and Clinical Immunology In Practice · doi:10.1016/j.jaip.2021.08.001 · Cited by 21 · see citing works
Self-citationEbo, D. G., Beyens, M. M. J., Heremans, K., van der Poorten, M. M., Gasse, A. L. V., Mertens, C. H., Houdt, M. V., Sabato, V., & Elst, J. (2022) · Current Pharmaceutical Design · doi:10.2174/1381612829666221025091827 · Cited by 21 · see citing works
Rijavec, M., Inkret, J., Bidovec‐Stojkovič, U., Carli, T., Frelih, N., Kukec, A., Korošec, P., & Košnik, M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242216368 · Cited by 21 · see citing works
Self-citationRama, T. A., Torrado, I., Henriques, A. F., Sánchez-Muñoz, L., Jara-Acevedo, M., Navarro-Navarro, P., Caldas, C., Mayado, A., Muñoz-González, J., García-Montero, A., et al. (2023) · The Journal of Allergy and Clinical Immunology: In Practice · doi:10.1016/j.jaip.2022.11.042 · Cited by 20 · see citing works
Diagnostic Significance of Tryptase for Suspected Mast Cell Disorders
Beyens, M., Toscano, A., Ebo, D., Gülen, T., & Sabato, V. (2023) · Diagnostics · doi:10.3390/diagnostics13243662 · Cited by 22 · see citing works
“There is a consensus that H α T is a risk modifier of severe anaphylaxis [21,48–53].”
BackgroundO’Connell, M. P., & Lyons, J. J. (2022) · Current Opinion in Allergy and Clinical Immunology · doi:10.1097/aci.0000000000000813 · Cited by 20 · see citing works
Self-citationUsing the Right Criteria for MCAS
Gülen, T. (2024) · Current Allergy and Asthma Reports · doi:10.1007/s11882-024-01126-0 · Cited by 20 · see citing works
Boyce, J. A. (2022) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2022.03.029 · Cited by 20 · see citing works
Venom Anaphylaxis: Decision Points for a More Aggressive Workup
Bonadonna, P., Korošec, P., Nalin, F., & Golden, D. B. K. (2023) · The Journal of Allergy and Clinical Immunology In Practice · doi:10.1016/j.jaip.2023.04.016 · Cited by 19 · see citing works
Self-citationBonadonna, P., Nalin, F., & Olivieri, F. (2022) · Current Opinion in Allergy & Clinical Immunology · doi:10.1097/aci.0000000000000849 · Cited by 18 · see citing works
Self-citationExtrinsic and Intrinsic Modulators of Anaphylaxis
Carter, M. C., Park, J., Vadas, P., & Worm, M. (2023) · The Journal of Allergy and Clinical Immunology In Practice · doi:10.1016/j.jaip.2023.05.015 · Cited by 17 · see citing works
Self-citationHow to evaluate the patient with a suspected mast cell disorder and how/when to manage symptoms
Akin, C. (2022) · Hematology · doi:10.1182/hematology.2022000366 · Cited by 17 · see citing works
The clinical features of hereditary alpha-tryptasemia
von Bubnoff, D., Koch, D., Stocker, H. R., Ludwig, R. J., Wortmann, F., & von Bubnoff, N. C. C. (2024) · Deutsches Ärzteblatt international · doi:10.3238/arztebl.m2023.0287 · Cited by 17 · see citing works
An update on anaphylaxis and urticaria
Worm, M., Vieths, S., & Mahler, V. (2022) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2022.10.014 · Cited by 17 · see citing works
Mast cell activation syndrome: is anaphylaxis part of the phenotype? A systematic review
Sabato, V., Michel, M., Blank, U., Ebo, D. G., & Vitte, J. (2021) · Current Opinion in Allergy and Clinical Immunology · doi:10.1097/aci.0000000000000768 · Cited by 16 · see citing works
Hereditary α-tryptasemia is Associated With Anaphylaxis to Antibiotics and Monoclonal Antibodies
Korošec, P., Lyons, J. J., Svetina, M., Koudová, M., Bittóova, M., Zidarn, M., Sedláčková, L., Rijavec, M., & Kopač, P. (2025) · The Journal of Allergy and Clinical Immunology In Practice · doi:10.1016/j.jaip.2025.04.013 · Cited by 16 · see citing works
Self-citationWhat Is the Value of Counting Mast Cells in Gastrointestinal Mucosal Biopsies?
Panarelli, N. C., Hornick, J. L., & Yantiss, R. K. (2023) · Modern Pathology · doi:10.1016/j.modpat.2022.100005 · Cited by 15 · see citing works
Golden, D. B. K. (2022) · Allergy and Asthma Proceedings · doi:10.2500/aap.2022.43.210109 · Cited by 15 · see citing works
Hymenoptera Venom Allergy and Anaphylaxis
Bilò, M. B., Martini, M., Danieli, M. G., & Moroncini, G. (2022) · Current Pharmaceutical Design · doi:10.2174/1381612828666220817091039 · Cited by 14 · see citing works
Knowledge gaps in the diagnosis and management of anaphylaxis
Wallace, D. V. (2023) · Annals of Allergy Asthma & Immunology · doi:10.1016/j.anai.2023.05.010 · Cited by 15 · see citing works
Risk Factors for Severe Sting Reactions and Side Effects During Venom Immunotherapy
Sturm, G. J., Schadelbauer, E., Marta, G., Bonadonna, P., & Košnik, M. (2024) · The Journal of Allergy and Clinical Immunology In Practice · doi:10.1016/j.jaip.2024.08.025 · Cited by 14 · see citing works
Self-citationGotlib, J. R., George, T. I., Carter, M. C., Austen, K. F., Bochner, B. S., Dwyer, D. F., Lyons, J. J., Hamilton, M. J., Butterfield, J. H., Bonadonna, P., et al. (2021) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2021.03.008 · Cited by 14 · see citing works
Self-citationHαT is associated with increased risk for severe Hymenoptera venom–triggered anaphylaxis
Šelb, J., Rijavec, M., Kopač, P., Lyons, J. J., & Korošec, P. (2022) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2022.11.017 · Cited by 14 · see citing works
Self-citationSystemic mastocytosis: 2023 update on diagnosis and management in adults
Costa, A. N., Scalzulli, E., Carmosino, I., Capriata, M., Ielo, C., Masucci, C., Passucci, M., Martelli, M., & Breccia, M. (2023) · Expert Opinion on Emerging Drugs · doi:10.1080/14728214.2023.2221028 · Cited by 13 · see citing works
Valent, P., Akin, C., & Arock, M. (2024) · Current Allergy and Asthma Reports · doi:10.1007/s11882-024-01124-2 · Cited by 13 · see citing works
- Authors
- Lyons, J. J., Chovanec, J., O’Connell, M. P., Liu, Y., Šelb, J., Zanotti, R., Bai, Y., Kim, J., Le, Q. T., DiMaggio, T., Schwartz, L. B., Komarow, H. D., Rijavec, M., Carter, M. C., Milner, J. D., Bonadonna, P., Metcalfe, D. D., & Korošec, P.
- Affiliations
- National Institutes of Health (US)
- University Clinic of Pulmonary and Allergic Diseases Golnik (SI)
- University of Verona (IT)
- Virginia Commonwealth University (US)
- Columbia University (US)
- Azienda Ospedaliera Universitaria Integrata Verona (IT)
- Corresponding author
- Lyons, Jonathan J.
- ORCID
- Venue
- Journal of Allergy and Clinical Immunology
- Publisher
- Elsevier BV
- Published
- 2021-02
- Volume
- 147
- Issue
- 2
- Pages
- 622-632
- ISSN
- 0091-6749 (ISSN-L)
- OpenAlex
- W3044735023
- Cited by
- 230
- References
- 33
- Citations by year
- 2026: 27 · 2025: 31 · 2024: 36 · 2023: 35 · 2022: 43 · 2021: 51 · 2020: 6
- FWCI
- 11.80
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Allergy and Clinical Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
- Health Sciences › Medicine › Immunology and Allergy › Food Allergy and Anaphylaxis Research
- Health Sciences › Medicine › Pharmacology › Drug-Induced Adverse Reactions
- Keywords
- hereditary alpha-tryptasemia, TPSAB1, copy number variation, systemic anaphylaxis, idiopathic anaphylaxis, systemic mastocytosis, hymenoptera venom allergy, protease-activated receptor 2, vascular permeability, droplet digital PCR
- MeSH terms
- Adolescent, Adult, Aged, Anaphylaxis, Arthropod Venoms, Child, Female, Genotype, Humans, Male, Middle Aged, Genetic Predisposition to Disease, Mastocytosis, Systemic, Tryptases, Young Adult, DNA Copy Number Variations
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