Detection of clonal mast cell disease in wasp venom allergic patients with normal tryptase
Open accessAbstract
Abstract Background Clonal mast cell disease (CMD) is an underlying aggravating condition in wasp venom allergy (WVA) which requires a different treatment strategy. CMD is increasingly recognized in patients with normal basal serum tryptase (bsT). However, methods to identify at risk patients have not yet been assessed in large cohorts of WVA patients with normal bsT. Methods This retrospective study evaluated the reliability of the REMA score in detecting CMD in a cohort of grade IV WVA patients with normal bsT and assessed the added value of other clinical parameters, KIT D816V mutation analysis in peripheral blood (PB) and the diagnosis of hereditary alpha tryptasemia (HAT). All patients had a conclusive bone marrow evaluation that demonstrated or excluded underlying CMD. Results In total 35 CMD and 96 non‐CMD patients were included. REMA score had a sensitivity of 72% (95% CI 56%–88%) and specificity of 79% (95% CI 70%–87%) in this cohort. Loss of consciousness during systemic reaction and bsT between 6.3 and 11.4 ng/ml were additional parameters independently associated with CMD. Sensitivity of KIT in PB was relatively low, 56% (95% CI 36%–75%), but had added value as screening method in patients with a low REMA score due to 100% specificity. Conclusion The REMA score is a relatively reliable method to detect patients at risk of CMD among WVA patients with normal bsT. KIT mutation analysis in PB could serve as additional screening method in patients with low REMA scores.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Even with a highly sensitive test, a negative result for the KIT D816V mutation in peripheral blood would not exclude underlying primary mast cell disorder, since this has a low negative predictive value.
“Importantly, even with a highly sensitive test, a negative result for the KIT D816V mutation in peripheral blood would not exclude underlying PMCD, since this has a low negative predictive value [68,69].”
From Diagnostic Significance of Tryptase for Suspected Mast Cell Disorders (2023) · cites this paper as [69]
The Results (KIT D816V mutation analysis in peripheral blood; page unavailable) report 55.6% sensitivity and patients with clonal mast cell disease who tested negative in peripheral blood, supporting the point that a negative result does not exclude disease. The study examined wasp-venom-allergic patients with normal basal tryptase; it does not report a negative predictive value or establish the claim for primary mast cell disorders generally. (LLM, conf=0.82)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
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
“SM is diagnosed according to the WHO criteria.(17) MMAS patients do not fulfill all SM criteria, but show mast cell clonality through a KIT mutation and/or aberrant expression of CD25 and/or CD2.”
MethodValent, 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 · cited 2× · see citing works
“According to current guidelines BME is indicated in all patients suspected of CMD.(18) As a positive KIT mutation in PB appears to affirm CMD, it could potentially be sufficient basis for lifelong VIT.”
MethodPrevention and treatment of hymenoptera venom allergy: guidelines for clinical practice
Bonifazi, F., Jutel, M., Bilò, M. B., Birnbaum, J., Müller, U., & the EAACI Interest Group on Insect Venom Hypersensitivity (2005) · Allergy · doi:10.1111/j.1398-9995.2005.00960.x · Cited by 420 · 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
Álvarez-Twose, I., González de Olano, D., Sánchez-Muñoz, L., Matito, A., Esteban-López, M. I., Vega, A., Mateo, M. B., Alonso Díaz de Durana, M. D., de la Hoz, B., del Pozo Gil, M. D., et al. (2010) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2010.02.019 · Cited by 294 · see citing works
Lyons, 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
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
Elberink, J. N. G. O., de Monchy, J. G. R., KORS, J. W., van Doormaal, J. J., & Dubois, A. E. J. (1997) · Journal of Allergy and Clinical Immunology · doi:10.1016/s0091-6749(97)70314-2 · Cited by 203 · see citing works
A Case of Intestinal Mastocytosis Misdiagnosed as Crohn's Disease
Reggiani, S., Cosso, L., Adriani, A., Pantaleoni, S., Risso, A., Vittone, F., Chiusa, L., Sapone, N., & Astegiano, M. (2015) · Case Reports in Gastroenterology · doi:10.1159/000430946 · Cited by 193 · see citing works
Alvarez-Twose, I., González-de-Olano, D., Sánchez-Muñoz, L., Matito, A., Jara-Acevedo, M., Teodosio, C., García-Montero, A., Morgado, J. M., Orfao, A., & Escribano, L. (2012) · International Archives of Allergy and Immunology · doi:10.1159/000329856 · Cited by 184 · see citing works
Insect Sting Allergy , Clinical Picture, Diagnosis, and Treatment
Mueller, U. R. (1990) · Cited by 182 · see citing works
Mastocytosis and insect venom allergy: diagnosis, safety and efficacy of venom immunotherapy
Niedoszytko, M., de Monchy, J., van Doormaal, J. J., Jassem, E., & Elberink, J. N. G. O. (2009) · Allergy · doi:10.1111/j.1398-9995.2009.02118.x · Cited by 158 · see citing works
Álvarez-Twose, I., Zanotti, R., González-de-Olano, D., Bonadonna, P., Vega, A., Matito, A., Sánchez-Muñoz, L., Morgado, J. M., Perbellini, O., García-Montero, A., et al. (2014) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2013.06.020 · Cited by 142 · see citing works
Zanotti, R., Lombardo, C., Passalacqua, G., Caimmi, C., Bonifacio, M., De Matteis, G., Perbellini, O., Rossini, M., Schena, D., Busa, M., et al. (2015) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2014.11.035 · Cited by 123 · see citing works
Bonadonna, P., González‐de‐Olano, D., Zanotti, R., Riccio, A., Ferrari, L. D., Lombardo, C., Rogkakou, A., Escribano, L., Álvarez‐Twöse, I., Matito, A., et al. (2013) · The Journal of Allergy and Clinical Immunology In Practice · doi:10.1016/j.jaip.2013.06.014 · Cited by 100 · see citing works
Carter, M. C., Desai, A., Komarow, H. D., Bai, Y., Clayton, S. T., Clark, A. S., Ruiz-Esteves, K. N., Long, L. M., Cantave, D., Wilson, T. M., et al. (2018) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2017.05.036 · Cited by 97 · 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
Bonadonna, P., Zanotti, R., Pagani, M., Bonifacio, M., Scaffidi, L., Olivieri, E., Franchini, M., Reccardini, F., Costantino, M. T., Roncallo, C., et al. (2018) · The Journal of Allergy and Clinical Immunology: In Practice · doi:10.1016/j.jaip.2017.11.025 · Cited by 73 · cited 3× · see citing works
“In recent years, however, the occurrence of CMD among patients with normal bsT has been increasingly recognized.(4,7) As the majority of HVA patients have normal bsT levels reliable screening methods for this group are highly important.”
BackgroundMethodŠelb, 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
Kristensen, T., Vestergaard, H., Bindslev‐Jensen, C., Mortz, C. G., Kjaer, H. F., Ollert, M., Møller, M. B., Broesby‐Olsen, S., & the Mastocytosis Centre Odense University Hospital (MastOUH) (2017) · Allergy · doi:10.1111/all.13187 · Cited by 38 · see citing works
Detection of an activating c-kit mutation by real-time PCR in patients with anaphylaxis
Lawley, W. J., Hird, H. J., Mallinder, P. R., McKenna, S., Hargadon, B., Murray, A. W. A., & Bradding, P. H. (2005) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2004.08.015 · Cited by 29 · see citing works
Diminished reliability of tryptase as risk indicator of mastocytosis in older overweight subjects
Vos, B. J. P. R., van der Veer, E., van Voorst Vader, P. C., Mulder, A. B., van der Heide, S., Arends, S., Kluin-Nelemans, J. C., de Monchy, J. G. R., van Doormaal, J. J., & Oude Elberink, J. N. G. (2015) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2014.05.047 · Cited by 17 · see citing works
Diagnosis of Primary Mast Cell Disorders in Anaphylaxis: Value of KIT D816V in Peripheral Blood
De Puysseleyr, L. P., Ebo, D. G., Elst, J., Faber, M. A., Poorten, M.-L. V. D., Van Gasse, A. L., Bridts, C. H., Mertens, C., Van Houdt, M., Hagendorens, M. M., et al. (2021) · The Journal of Allergy and Clinical Immunology In Practice · doi:10.1016/j.jaip.2021.04.062 · Cited by 13 · see citing works
Golden, D. B. K. (2019) · Immunology and Allergy Clinics of North America · doi:10.1016/j.iac.2019.09.002 · Cited by 11 · see citing works
Flagged first, then by citations
1 of the 26 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
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
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
“Importantly, even with a highly sensitive test, a negative result for the KIT D816V mutation in peripheral blood would not exclude underlying PMCD, since this has a low negative predictive value [68,69].”
BackgroundDisease Spectrum of Anaphylaxis Disorders
González de Olano, D., Cain, W. V., Bernstein, J. A., & Akin, C. (2023) · The Journal of Allergy and Clinical Immunology In Practice · doi:10.1016/j.jaip.2023.05.012 · Cited by 19 · see citing works
Alheraky, A., Meijer, K., Nijk, M. T., Klein, S. K., Elberink, H. O., Kema, I. P., & Mulder, A. B. (2025) · Cytometry Part A · doi:10.1002/cyto.a.24950 · Cited by 5 · see citing works
Alheraky, A., Simpelaar, A., Hesp, L. B., Wierenga, A. T. J., Heddema, M., Minović, I., Klein, S. K., Elberink, H. N. G. O., Kema, I. P., & Mulder, A. B. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27146314 · Cited by 1 · see citing works
An Approach to the Bone Marrow Workup and Diagnosis of Eosinophilia and Mast Cell Disorders
Reichard, K. K., George, T. I., & Arber, D. A. (2025) · Advances in Anatomic Pathology · doi:10.1097/pap.0000000000000486
Alheraky, A., Meijer, K., Nijk, M. T., Klein, S. K., Elberink, H. N. G. O., Kema, I. P., & Mulder, A. B. (2026) · Cytometry Part B Clinical Cytometry · doi:10.1002/cyto.b.70071
- Authors
- Onnes, M. C., Alheraky, A., Nawijn, M. C., Sluijter, T. E., Mulder, A. B., Arends, S., & Oude Elberink, H. N. G.
- Affiliations
- University Medical Center Groningen (NL)
- Department of Internal Medicine Division of Allergology University Medical Center Groningen University of Groningen Groningen The Netherlands
- Corresponding author
- Onnes, Merel C.
- ORCID
- Venue
- Clinical and Translational Allergy
- Publisher
- Wiley
- Published
- 2022-09
- Volume
- 12
- Issue
- 9
- Pages
- e12174-e12174
- ISSN
- 2045-7022 (ISSN-L)
- PMC
- PMC9449818
- OpenAlex
- W4294936157
- Cited by
- 8
- References
- 26
- Citations by year
- 2026: 2 · 2025: 2 · 2023: 3 · 2022: 1
- FWCI
- 0.57
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Clinical and Translational Allergy (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- 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 › Immunology and Allergy › Allergic Rhinitis and Sensitization
- Keywords
- wasp venom allergy, KIT D816V mutation, hereditary alpha-tryptasemia, screening, bone marrow examination, systemic reactions, mast cell activation
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
