| Title: | High burden of clonal mast cell disorders and hereditary ▫$α-tryptasemia$▫ in patients who need Hymenoptera venom immunotherapy |
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| Authors: | ID Korošec, Peter, Univerzitetna klinika za pljučne bolezni in alergijo Golnik (Author)
ID Sturm, Gunter (Author)
ID Lyons, Jonathan J. (Author)
ID Pirc Marolt, Tinkara, Univerzitetna klinika za pljučne bolezni in alergijo Golnik (Author)
ID Svetina, Manca (Author)
ID Košnik, Mitja, Univerzitetna klinika za pljučne bolezni in alergijo Golnik (Author)
ID Zidarn, Mihaela, Univerzitetna klinika za pljučne bolezni in alergijo Golnik (Author)
ID Kačar, Mark, Univerzitetna klinika za pljučne bolezni in alergijo Golnik (Author)
ID Frelih, Nina, Univerzitetna klinika za pljučne bolezni in alergijo Golnik (Author)
ID Lalek, Nika, Univerzitetna klinika za pljučne bolezni in alergijo Golnik (Author)
ID Demšar Luzar, Ajda, Univerzitetna klinika za pljučne bolezni in alergijo Golnik (Author)
ID Zver, Samo (Author)
ID Škerget, Matevž (Author)
ID Czarnobilska, Ewa (Author)
ID Dyga, Wojciech (Author)
ID Popović-Grle, Sanja (Author)
ID Samaržija, Miroslav (Author)
ID Arzt-Gradwohl, Lisa (Author)
ID Čerpes, Urban (Author)
ID Porebski, Grzegorz (Author)
ID Pevec, Branko (Author)
ID Schadelbauer, Eva (Author)
ID Kopač, Peter, Univerzitetna klinika za pljučne bolezni in alergijo Golnik (Author)
ID Šelb, Julij, Univerzitetna klinika za pljučne bolezni in alergijo Golnik (Author)
ID Rijavec, Matija, Univerzitetna klinika za pljučne bolezni in alergijo Golnik (Author), et al. |
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| Files: |  URL - Source URL, visit https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.16084
 PDF - Presentation file, download (7,30 MB)
MD5: 186497D0D27EE21DB0B91CF4F9B32873
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| Language: | English |
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| Typology: | 1.01 - Original Scientific Article |
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| Organization: |  UKPBAG - University Clinic of Respiratory and Allergic Diseases Golnik
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| Abstract: | Background
In patients who require venom immunotherapy (VIT), there is a need to identify underlying mast cell (MC) disorders since these may affect the risk and severity of future sting reactions and the long-term effectiveness of VIT.
Methods
1319 individuals with Hymenoptera venom allergy (HVA) who needed VIT from referral centers in Slovenia, Austria, Croatia, and Poland underwent examination for KIT p.D816V in peripheral blood leukocytes (PBL) using a highly sensitive PCR test and tryptase genotyping by digital droplet PCR. We also included 183 control individuals with large local reactions (LLRs) to Hymenoptera stings and with asymptomatic sensitization to Hymenoptera venoms.
Results
285 of 1319 individuals recommended for VIT (21.6%) were positive for KIT p.D816V in PBL, preferably those who present with severe reaction (33.9% [n = 207 of 610] with Ring-Messmer grade 3–4 vs. 11% [n = 78 of 709] with Grade 1–2; p < .0001), whereas only 1.3% (n = 2 of 152) of controls with LLR and none with asymptomatic sensitization (n = 31) had KIT p.D816V. KIT p.D816V allelic burden was higher in those with severe reaction (median 0.018% [n = 207] in Grade 3–4 vs. 0.001% [n = 78] in Grade 1–2; p < .0001), and the majority had normal baseline serum tryptase levels (69% [n = 196 of 285]). All KIT p.D816V-positive individuals (n = 41) who underwent bone marrow (BM) biopsy were found to have underlying clonal diseases, principally BM mastocytosis. HαT was also associated with severe HVA and symptoms (p < .01), and remarkably, 31.0% (n = 31 of 100) were found to have concomitant KIT p.D816V. Concomitant HαT and KIT p.D816V showed an additive effect, and having both was associated with the highest risk for severe HVA, even higher than having either HαT or KIT p.D816V alone (OR = 3.8; p < .01).
Conclusions
By employing prospective universal tryptase genotyping and examination for KIT p.D816V in PBL in large HVA populations, we have demonstrated a high burden of clonal MC disorders and HαT in patients who require VIT. |
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| Keywords: | anaphylaxis, hereditary α-tryptasemia, hypersensitivity, immunotherapy, mast cell, mastocytosis, venom |
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| Publication status: | Published |
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| Publication version: | Version of Record |
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| Submitted for review: | 23.11.2023 |
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| Article acceptance date: | 14.02.2024 |
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| Publication date: | 01.09.2024 |
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| Publisher: | Wiley-Blackwell |
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| Year of publishing: | 2024 |
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| Number of pages: | str. 1-12 |
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| Source: | Allergy |
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| PID: | 20.500.12556/DiRROS-19111  |
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| UDC: | 616-097 |
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| ISSN on article: | 1398-9995 |
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| DOI: | 10.1111/all.16084 |
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| COBISS.SI-ID: | 190093315 |
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| Copyright: | © 2024 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd. |
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| Note: | Opis z dne 25. 3. 2024;
Nasl. z nasl. zaslona;
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| Publication date in DiRROS: | 17.06.2024 |
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| Views: | 516 |
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| Downloads: | 312 |
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