20.500.12556/DiRROS-19111 High burden of clonal mast cell disorders and hereditary ▫$α-tryptasemia$▫ in patients who need Hymenoptera venom immunotherapy 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. anaphylaxis hereditary α-tryptasemia hypersensitivity immunotherapy mast cell mastocytosis venom anafilaksija dedna α-triptazemija preobčutljivost imunoterapija mastociti mastocitoza strupi kožekrilcev true false true Wiley-Blackwell Allergy Angleški jezik Slovenski jezik © 2024 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd. Neznano 2024-06-17 13:48:13 2024-06-17 13:48:13 2025-02-17 10:07:23 0000-00-00 00:00:00 2024 0 0 Opis z dne 25. 3. 2024; Nasl. z nasl. zaslona; str. 1-12 13. Mar. 2024 0000-00-00 Zaloznikova Objavljeno NiDoloceno 2023-11-23 2024-02-14 2024-09-01 616-097 1398-9995 10.1111/all.16084 190093315 https://onlinelibrary.wiley.com/doi/epdf/10.1111/all.16084 1 7b39124e-2c9f-11ef-9c9e-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=26292 RAZ_Korosec_Peter_2024.pdf RAZ_Korosec_Peter_2024.pdf 1 186497D0D27EE21DB0B91CF4F9B32873 1107dfc862ba795c142ca9ef4f85e509a81966d5291fd460ce2ae4cea91d7343 d3ed2b05-70cc-11ef-9d3a-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=28732 Univerzitetna klinika za pljučne bolezni in alergijo Golnik 0 0 0