Clinical impact of the TPSAB1 genotype in mast cell diseases: A REMA study in a cohort of 959 individuals
Open accessAbstract
Background: A close association between hereditary alpha‐tryptasemia (HAT) and mast cell (MC) disorders has been previously reported. However, the relationship between HAT and the diagnostic subtypes and clinical features of MC disorders still remains to be established. Objective: To determine the prevalence of HAT in healthy donors (HD) vs patients with different diagnostic subtypes of MC activation syndromes (MCAS) and mastocytosis, and its relationship with the clinical behavior of the disease. Methods: A total of 959 subjects were studied including 346 healthy donors (HD), 464 mastocytosis, and 149 non‐clonal MCAS patients. Molecular studies to assess the TPSAB1 genotype were performed, and data on serum baseline tryptase (sBT) and basal MC‐mediator release episodes and triggers of anaphylaxis were collected. Results: HAT was detected in 15/346 (4%) HD versus 43/149 (29%) non‐clonal MCAS and 84/464 (18%) mastocytosis cases. Among mastocytosis, HAT was more frequently found in patients with MC‐restricted KITD816V (21% vs. 10% among multilineage KITD816V patients; p = .008). Overall, median sBT was higher in cases presenting with HAT (28.9 vs. 24.5 ng/mL; p = .008), while no significant differences in sBT were observed among HAT+ mastocytosis patients depending on the presence of 1 vs. ≥2 extra copies of the α‐tryptase gene (44.1 vs. 35.2 ng/mL, p > .05). In turn, anaphylaxis was more frequently observed in HAT+ versus HAT− mastocytosis patients (76% vs. 65%; p = .018), while HAT+ and HAT− patients who did not refer anaphylaxis as the presenting symptom (n = 308) showed a similar prevalence of subsequent anaphylaxis (35% vs. 36%, respectively). Conclusion: The frequency of HAT in MC disorders varies according to the diagnostic subtype of the disease. HAT does not imply a higher risk (and severity) of anaphylaxis in mastocytosis patients in whom anaphylaxis is not part of the presenting symptoms of the disease.
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A recent study did not find a difference in the prevalence of HαT in patients with or without anaphylaxis with underlying systemic mastocytosis.
“However, a recent study did not find a difference in the prevalence of HαT in patients with or without anaphylaxis with underlying SM [54], and more studies with opposing results exist [55].”
From Diagnostic Significance of Tryptase for Suspected Mast Cell Disorders (2023) · cites this paper as [54]
Section 3.1 reports no statistically significant difference in HαT prevalence between mastocytosis patients with and without concomitant MCAS (20% vs. 15%), and the Discussion says an increased anaphylaxis risk could not be confirmed among mastocytosis cases. However, MCAS is not identical to anaphylaxis, and the paper also reports more anaphylaxis among HαT-positive than HαT-negative mastocytosis patients (76% vs. 65%; p = .018). The unqualified claim therefore misses a conflicting result in the source. (LLM, conf=0.82)
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Cites
Arber, D. A., Orazi, A., Hasserjian, R., Thiele, J., Borowitz, M. J., Le Beau, M. M., Bloomfield, C. D., Cazzola, M., & Vardiman, J. W. (2016) · Blood · doi:10.1182/blood-2016-03-643544 · Cited by 10,119 · cited 1× · see citing works
“23,24”
Arber, D. A., Orazi, A., Hasserjian, R. P., Borowitz, M. J., Calvo, K. R., Kvasnicka, H.-M., Wang, S. A., Bagg, A., Barbui, T., Branford, S., et al. (2022) · Blood · doi:10.1182/blood.2022015850 · Cited by 2,945 · see citing works
Self-citationSampson, H. A., Muñoz‐Furlong, A., Campbell, R. L., Adkinson, N. F., Bock, S. A., Branum, A. M., Brown, S. G. A., Camargo, C. A., Cydulka, R. K., Galli, S. J., et al. (2006) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2005.12.1303 · Cited by 2,308 · see citing works
Tryptase levels as an indicator of mast-cell activation in systemic anaphylaxis and mastocytosis
Schwartz, L. B., Metcalfe, D. D., Miller, J. S., Earl, H., & Sullivan, T. (1987) · New England Journal of Medicine · doi:10.1056/nejm198706253162603 · Cited by 784 · see citing works
Valent, P., Akin, C., Escribano, L., Födinger, M., Hartmann, K., Brockow, K., Castells, M., Sperr, W. R., Kluin‐Nelemans, H. C., Hamdy, N. A. T., et al. (2007) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.2007.01807.x · Cited by 750 · see citing works
García‐Montero, A. C. (2006) · Blood · doi:10.1182/blood-2006-04-015545 · Cited by 502 · see citing works
Self-citationTryptase from human pulmonary mast cells. Purification and characterization
Schwartz, L. B., Lewis, R. A., & Austen, K. F. (1981) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)68496-6 · Cited by 419 · 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
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-citationLyons, J. J., Chovanec, J., O’Connell, M. P., Liu, Y., Šelb, J., Zanotti, R., Bai, Y., Kim, J., Le, Q. T., DiMaggio, T., et al. (2021) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2020.06.035 · Cited by 230 · see citing works
Human mast cell tryptase: multiple cDNAs and genes reveal a multigene serine protease family.
Vanderslice, P., Ballinger, S. M., Tam, E. K., Goldstein, S., Craik, C. S., & Caughey, G. H. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.10.3811 · Cited by 227 · see citing works
Kristensen, T., Vestergaard, H., & Møller, M. B. (2011) · The Journal of Molecular Diagnostics · doi:10.1016/j.jmoldx.2010.10.004 · Cited by 208 · see citing works
Sperr, W. R., Jordan, J.-H., Fiegl, M., Escribano, L., Bellas, C., Dirnhofer, S., Semper, H., Simonitsch-Klupp, I., Horny, H.-P., & Valent, P. (2002) · International Archives of Allergy and Immunology · doi:10.1159/000059404 · Cited by 207 · see citing works
Greiner, 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
Systemic mastocytosis in adults: 2021 Update on diagnosis, risk stratification and management
Pardanani, A. D. (2021) · American Journal of Hematology · doi:10.1002/ajh.26118 · Cited by 181 · see citing works
Lyons, J. J. (2018) · Immunology and Allergy Clinics of North America · doi:10.1016/j.iac.2018.04.003 · Cited by 179 · 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
Escribano, L., Dı́az-Agustı́n, B., López, A., Núñez, R., García‐Montero, A. C., Almeida, J., Prados, A., Angulo, M., Herrero, S., Órfão, A., et al. (2004) · Cytometry Part B Clinical Cytometry · doi:10.1002/cyto.b.10072 · Cited by 148 · see citing works
Self-citationTeodósio, C., García‐Montero, A. C., Jara‐Acevedo, M., Sánchez‐Muñoz, L., Álvarez‐Twöse, I., Núñez, R., Schwartz, L. B., Walls, A. F., Escribano, L., & Órfão, A. (2010) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2009.10.020 · Cited by 138 · see citing works
Self-citationLyons, 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
Corbisier, P., Pinheiro, L. B., Stephane, M., Kortekaas, A.-M., Chung, P. Y. J., Gerganova, T., Roebben, G., Emons, H., & Emslie, K. R. (2015) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-015-8458-z · Cited by 133 · 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
Hereditary alpha-tryptasemia: UK prevalence and variability in disease expression
Robey, R. C., Wilcock, A., Bonin, H., Beaman, G., Myers, B., Grattan, C., Briggs, T. A., & Arkwright, P. D. (2020) · The Journal of Allergy and Clinical Immunology In Practice · doi:10.1016/j.jaip.2020.05.057 · Cited by 119 · see citing works
Anaphylaxis and anaphylactoid reactions
Ring, J., & Behrendt, H. (1999) · Clinical Reviews in Allergy & Immunology · doi:10.1007/bf02737644 · Cited by 110 · see citing works
Hoermann, G., Gleixner, K. V., Dinu, G. E., Kundi, M., Greiner, G., Wimazal, F., Hadzijusufovic, E., Mitterbauer, G., Mannhalter, C., Valent, P., et al. (2014) · Allergy · doi:10.1111/all.12409 · Cited by 106 · 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
Assessment of the real-time PCR and different digital PCR platforms for DNA quantification
Pavšič, J., Žel, J., & Milavec, M. (2015) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-015-9107-2 · Cited by 90 · see citing works
Hereditary 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
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
Giannetti, 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
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
Valent, 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
Hymenoptera 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
Familial hypertryptasemia with associated mast cell activation syndrome
Sabato, V., Van De Vijver, E., Hagendorens, M., Vrelust, I., Reyniers, E., Fransen, E., Bridts, C., De Clerck, L., Mortier, G., Valent, P., et al. (2014) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2014.06.007 · Cited by 52 · see citing works
Inherited 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
Sordi, 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
Incorporating 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
Sánchez‐Muñoz, L., Teodósio, C., Morgado, J. M., & Escribano, L. (2011) · Methods in cell biology · doi:10.1016/b978-0-12-385493-3.00014-0 · Cited by 44 · 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
Classification and Pathophysiology
Johnson, W. H., & Moller, J. H. (2008) · Pediatric Cardiology · doi:10.1002/9781444300697.ch3 · Cited by 38 · see citing works
Mast cell activation in the context of elevated basal serum tryptase: genetics and presentations
Khoury, P., & Lyons, J. J. (2019) · Current Allergy and Asthma Reports · doi:10.1007/s11882-019-0887-x · Cited by 30 · see citing works
Differential 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
Current state of biology and diagnosis of clonal mast cell diseases in adults
Álvarez‐Twöse, I., Morgado, J. M., Sánchez‐Muñoz, L., García‐Montero, A. C., Mollejo, M., Orfao, A., & ESCRIBANO, L. (2012) · International Journal of Laboratory Hematology · doi:10.1111/j.1751-553x.2012.01427.x · Cited by 21 · see citing works
Self-citationIncreased TPSAB1 Copy Number in a Family With Elevated Basal Serum Levels of Tryptase
Hernández-Hernández, L., Sanz, C., Marcos-Vadillo, E., Garcı́a-Sánchez, A., Moreno, E. S., Lorente, F., González‐de‐Olano, D., Davila, I. J., & Isidoro‐García, M. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.577081 · Cited by 5 · see citing works
Self-citationHereditary alpha tryptasemia in identical twins
Bethea, L. H., Tuano, K. S., Seth, N., & Chinen, J. (2021) · Annals of Allergy Asthma & Immunology · doi:10.1016/j.anai.2021.06.011 · Cited by 1 · see citing works
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Research works printed but not linked: 2
- Arber DA, Orazi A, Hasserjian RP, et al. International consen- sus classification of myeloid neoplasms and acute Leukemias- integratingmorphologic, clinical, and genomic data. Blood. 2022;140(11):1200-1228.
- Hoermann G, Gleixner KV, Dinu GE, et al. The KIT D816V allele bur- den predicts survival in patients with mastocytosis and correlates with the WHO type of the disease. Allergy. 2014;69(6):810-813.
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Shin, H., & Lyons, J. J. (2024) · Current Allergy and Asthma Reports · doi:10.1007/s11882-024-01136-y · Cited by 24 · 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
McMurray, J. C., Pacheco, C. S., Schornack, B. J., Sun, X., Brunader, J. A., Scott, A. E., Ariza, J. S., Kou, C.-T. J., Costantino, R. C., Pittman, L. M., et al. (2024) · Blood · doi:10.1182/blood.2023023347 · Cited by 11 · see citing works
- Authors
- 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., Orfao, A., & Álvarez‐Twose, I.
- Affiliations
- Instituto Ramón y Cajal de Investigación Sanitaria (ES)
- Universidad de Salamanca (ES)
- Centro de Investigación Biomédica en Red de Cáncer (ES)
- Hospital Virgen del Valle (ES)
- Instituto de Investigación Biomédica de Salamanca (ES)
- Spanish Network on Mastocytosis (REMA), Toledo and Salamanca Salamanca Spain
- ORCID
- Venue
- Allergy
- Publisher
- Wiley
- Published
- 2023-10-11
- Volume
- 79
- Issue
- 3
- Pages
- 711-723
- ISSN
- 0105-4538 (ISSN-L)
- 1398-9995
- OpenAlex
- W4387563545
- Cited by
- 38
- References
- 45
- Citations by year
- 2026: 11 · 2025: 13 · 2024: 12 · 2023: 2
- FWCI
- 4.17
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Allergy (publishedVersion)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Funders
- Instituto de Salud Carlos III
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
- Health Sciences › Medicine › Surgery › Congenital gastrointestinal and neural anomalies
- Health Sciences › Medicine › Hematology › Platelet Disorders and Treatments
- Keywords
- hereditary alpha-tryptasemia, mast cell activation syndrome, mastocytosis, KIT D816V mutation, serum tryptase, anaphylaxis, mast cell mediators, disease severity, healthy donors
- MeSH terms
- Mast Cell Activation Syndrome, Anaphylaxis, Genotype, Humans, Mast Cells, Mastocytosis, Tryptases
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