Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
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SHR Neuro Krebs Kardio Lipid Stoffw Microb
Korošec, P; Sturm, GJ; Lyons, JJ; Marolt, TP; Svetina, M; Košnik, M; Zidarn, M; Kačar, M; Frelih, N; Lalek, N; Luzar, AD; Zver, S; Škerget, M; Czarnobilska, E; Dyga, W; Grle, SP; Samarzija, M; Arzt-Gradwohl, L; Čerpes, U; Porebski, G; Pevec, B; Schadelbauer, E; Kopač, P; Šelb, J; Rijavec, M.
High burden of clonal mast cell disorders and hereditary α-tryptasemia in patients who need Hymenoptera venom immunotherapy.
Allergy. 2024; 79(9):2458-2469
Doi: 10.1111/all.16084
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- Co-Autor*innen der Med Uni Graz
- Arzt-Gradwohl Lisa
- Cerpes Urban
- Schadelbauer Eva
- Sturm Gunter
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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.
- Find related publications in this database (using NLM MeSH Indexing)
- Humans - administration & dosage
- Arthropod Venoms - immunology
- Tryptases - blood
- Male - administration & dosage
- Female - administration & dosage
- Hymenoptera - immunology
- Adult - administration & dosage
- Desensitization, Immunologic - methods
- Middle Aged - administration & dosage
- Animals - administration & dosage
- Mastocytosis - therapy, genetics, diagnosis
- Young Adult - administration & dosage
- Adolescent - administration & dosage
- Mast Cells - immunology
- Proto-Oncogene Proteins c-kit - genetics
- Aged - administration & dosage
- Child - administration & dosage
- Insect Bites and Stings - therapy, immunology
- Hypersensitivity - therapy, diagnosis
- Genotype - administration & dosage
- Child, Preschool - administration & dosage
- Find related publications in this database (Keywords)
- anaphylaxis
- hereditary alpha-tryptasemia
- hypersensitivity
- immunotherapy
- mast cell
- mastocytosis
- venom