High burden of clonal mast cell disorders and hereditary α-tryptasemia in patients who need Hymenoptera venom immunotherapy

Korošec, Peter (author), Sturm, Gunter J. (author), Lyons, Jonathan J. (author), Pirc Marolt, Tinkara (author), Svetina, Manca (author), Košnik, Mitja (author), Zidarn, Mihaela (author), Kačar, Mark (author), Frelih, Nina (author), Lalek, Nika (author), Demšar Luzar, Ajda (author), Zver, Samo (author), Škerget, Matevž (author), Czarnobilska, Ewa (author), Dyga, Wojciech (author), Popović-Grle, Sanja (author), Samaržija, Miroslav (author), Arzt-Gradwohl, Lisa (author), Čerpes, Urban (author), Porebski, Grzegorz (author), Pevec, Branko (author), Schadelbauer, Eva (author), Kopač, Peter (author), Šelb, Julij (author), Rijavec, Matija (author)

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.

• Language: English
• Keywords: anaphylaxis, hereditary α-tryptasemia, hypersensitivity, immunotherapy, mast cell, mastocytosis, venom
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy; BF - Biotechnical Faculty; MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2024
• Number of pages: Str. 2458-2469
• Numbering: Vol. 79, iss 9
• PID: 20.500.12556/RUL-161033-a6532f51-3f82-841d-8e60-995ad104ad20
• UDC: 616-097
• ISSN on article: 1398-9995
• DOI: 10.1111/all.16084
• COBISS.SI-ID: 190093315
• Publication date in RUL: 06.09.2024

Record is a part of a journal

• Title: Allergy
• Publisher: Wiley, European Academy of Allergy and Clinical Immunology
• ISSN: 1398-9995
• COBISS.SI-ID: 515009305

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: anafilaksija, dedna α-triptazemija, preobčutljivost, imunoterapija, mastociti, mastocitoza, strupi kožekrilcev