학술논문
High burden of clonal mast cell disorders and hereditary α-tryptasemia in patients who need Hymenoptera venom immunotherapy.
Document Type
Academic Journal
Author
Korošec P; University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia.; Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia.; Faculty of Medicine, University of Maribor, Maribor, Slovenia.; Sturm GJ; Department of Dermatology and Venerology, Medical University of Graz, Graz, Austria.; Allergy Outpatient Clinic Reumannplatz, Vienna, Austria.; Lyons JJ; Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.; Marolt TP; University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia.; Svetina M; University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia.; Biotechnical Faculty, University of Ljubljana, Ljubljana, Slovenia.; Košnik M; University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia.; Medical Faculty, University of Ljubljana, Ljubljana, Slovenia.; Zidarn M; University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia.; Biotechnical Faculty, University of Ljubljana, Ljubljana, Slovenia.; Medical Faculty, University of Ljubljana, Ljubljana, Slovenia.; Kačar M; University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia.; Medical Faculty, University of Ljubljana, Ljubljana, Slovenia.; Frelih N; University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia.; Medical Faculty, University of Ljubljana, Ljubljana, Slovenia.; Lalek N; University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia.; Medical Faculty, University of Ljubljana, Ljubljana, Slovenia.; Luzar AD; University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia.; Biotechnical Faculty, University of Ljubljana, Ljubljana, Slovenia.; Zver S; Medical Faculty, University of Ljubljana, Ljubljana, Slovenia.; The Department of Hematology, University Medical Center Ljubljana, Ljubljana, Slovenia.; Škerget M; Medical Faculty, University of Ljubljana, Ljubljana, Slovenia.; The Department of Hematology, University Medical Center Ljubljana, Ljubljana, Slovenia.; Czarnobilska E; Department of Clinical and Environmental Allergology, Jagiellonian University Medical College, Krakow, Poland.; Dyga W; Department of Clinical and Environmental Allergology, Jagiellonian University Medical College, Krakow, Poland.; Grle SP; Clinic for Respiratory Diseases Jordanovac, University Hospital Centre Zagreb, Zagreb, Croatia.; Samarzija M; Clinic for Respiratory Diseases Jordanovac, University Hospital Centre Zagreb, Zagreb, Croatia.; Arzt-Gradwohl L; Department of Dermatology and Venerology, Medical University of Graz, Graz, Austria.; Čerpes U; Department of Dermatology and Venerology, Medical University of Graz, Graz, Austria.; Porebski G; Department of Clinical and Environmental Allergology, Jagiellonian University Medical College, Krakow, Poland.; Pevec B; Clinic for Respiratory Diseases Jordanovac, University Hospital Centre Zagreb, Zagreb, Croatia.; Schadelbauer E; Department of Dermatology and Venerology, Medical University of Graz, Graz, Austria.; Kopač P; University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia.; Medical Faculty, University of Ljubljana, Ljubljana, Slovenia.; Šelb J; University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia.; Medical Faculty, University of Ljubljana, Ljubljana, Slovenia.; Rijavec M; University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia.; Biotechnical Faculty, University of Ljubljana, Ljubljana, Slovenia.
Source
Publisher: Wiley-Blackwell Country of Publication: Denmark NLM ID: 7804028 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1398-9995 (Electronic) Linking ISSN: 01054538 NLM ISO Abbreviation: Allergy Subsets: MEDLINE
Subject
Language
English
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.
(© 2024 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)
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.
(© 2024 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)