{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T06:50:45Z","timestamp":1791528645363,"version":"4.3.4"},"reference-count":59,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T00:00:00Z","timestamp":1710288000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004329","name":"Javna Agencija za Raziskovalno Dejavnost RS","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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\u2010term effectiveness of VIT.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      1319 individuals with Hymenoptera venom allergy (HVA) who needed VIT from referral centers in Slovenia, Austria, Croatia, and Poland underwent examination for\n                      <jats:italic>KIT<\/jats:italic>\n                      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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      285 of 1319 individuals recommended for VIT (21.6%) were positive for\n                      <jats:italic>KIT<\/jats:italic>\n                      p.D816V in PBL, preferably those who present with severe reaction (33.9% [\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009207 of 610] with Ring\u2010Messmer grade 3\u20134 vs. 11% [\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200978 of 709] with Grade 1\u20132;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.0001), whereas only 1.3% (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20092 of 152) of controls with LLR and none with asymptomatic sensitization (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200931) had\n                      <jats:italic>KIT<\/jats:italic>\n                      p.D816V.\n                      <jats:italic>KIT<\/jats:italic>\n                      p.D816V allelic burden was higher in those with severe reaction (median 0.018% [\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009207] in Grade 3\u20134 vs. 0.001% [\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200978] in Grade 1\u20132;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.0001), and the majority had normal baseline serum tryptase levels (69% [\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009196 of 285]). All\n                      <jats:italic>KIT<\/jats:italic>\n                      p.D816V\u2010positive individuals (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200941) who underwent bone marrow (BM) biopsy were found to have underlying clonal diseases, principally BM mastocytosis. H\u03b1T was also associated with severe HVA and symptoms (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.01), and remarkably, 31.0% (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200931 of 100) were found to have concomitant\n                      <jats:italic>KIT<\/jats:italic>\n                      p.D816V. Concomitant H\u03b1T and\n                      <jats:italic>KIT<\/jats:italic>\n                      p.D816V showed an additive effect, and having both was associated with the highest risk for severe HVA, even higher than having either H\u03b1T or\n                      <jats:italic>KIT<\/jats:italic>\n                      p.D816V alone (OR\u2009=\u20093.8;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.01).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      By employing prospective universal tryptase genotyping and examination for\n                      <jats:italic>KIT<\/jats:italic>\n                      p.D816V in PBL in large HVA populations, we have demonstrated a high burden of clonal MC disorders and H\u03b1T in patients who require VIT.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/all.16084","type":"journal-article","created":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T08:25:46Z","timestamp":1710318346000},"page":"2458-2469","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["High burden of clonal mast cell disorders and hereditary \u03b1\u2010tryptasemia in patients who need\n                    <i>Hymenoptera<\/i>\n                    venom immunotherapy"],"prefix":"10.1111","volume":"79","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0835-1599","authenticated-orcid":false,"given":"Peter","family":"Koro\u0161ec","sequence":"first","affiliation":[{"name":"University Clinic of Respiratory and Allergic Diseases  Golnik Slovenia"},{"name":"Faculty of Pharmacy University of Ljubljana  Ljubljana Slovenia"},{"name":"Faculty of Medicine University of Maribor  Maribor Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7245-121X","authenticated-orcid":false,"given":"Gunter J.","family":"Sturm","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venerology Medical University of Graz  Graz Austria"},{"name":"Allergy Outpatient Clinic Reumannplatz  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan J.","family":"Lyons","sequence":"additional","affiliation":[{"name":"Laboratory of Allergic Diseases National Institute of Allergy and Infectious Diseases, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tinkara Pirc","family":"Marolt","sequence":"additional","affiliation":[{"name":"University Clinic of Respiratory and Allergic Diseases  Golnik Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manca","family":"Svetina","sequence":"additional","affiliation":[{"name":"University Clinic of Respiratory and Allergic Diseases  Golnik Slovenia"},{"name":"Biotechnical Faculty University of Ljubljana  Ljubljana Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4701-7374","authenticated-orcid":false,"given":"Mitja","family":"Ko\u0161nik","sequence":"additional","affiliation":[{"name":"University Clinic of Respiratory and Allergic Diseases  Golnik Slovenia"},{"name":"Medical Faculty University of Ljubljana  Ljubljana Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihaela","family":"Zidarn","sequence":"additional","affiliation":[{"name":"University Clinic of Respiratory and Allergic Diseases  Golnik Slovenia"},{"name":"Biotechnical Faculty University of Ljubljana  Ljubljana Slovenia"},{"name":"Medical Faculty University of Ljubljana  Ljubljana Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Ka\u010dar","sequence":"additional","affiliation":[{"name":"University Clinic of Respiratory and Allergic Diseases  Golnik Slovenia"},{"name":"Medical Faculty University of Ljubljana  Ljubljana Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Frelih","sequence":"additional","affiliation":[{"name":"University Clinic of Respiratory and Allergic Diseases  Golnik Slovenia"},{"name":"Medical Faculty University of Ljubljana  Ljubljana Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nika","family":"Lalek","sequence":"additional","affiliation":[{"name":"University Clinic of Respiratory and Allergic Diseases  Golnik Slovenia"},{"name":"Medical Faculty University of Ljubljana  Ljubljana Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajda Dem\u0161ar","family":"Luzar","sequence":"additional","affiliation":[{"name":"University Clinic of Respiratory and Allergic Diseases  Golnik Slovenia"},{"name":"Biotechnical Faculty University of Ljubljana  Ljubljana Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samo","family":"Zver","sequence":"additional","affiliation":[{"name":"Medical Faculty University of Ljubljana  Ljubljana Slovenia"},{"name":"The Department of Hematology University Medical Center Ljubljana  Ljubljana Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matev\u017e","family":"\u0160kerget","sequence":"additional","affiliation":[{"name":"Medical Faculty University of Ljubljana  Ljubljana Slovenia"},{"name":"The Department of Hematology University Medical Center Ljubljana  Ljubljana Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewa","family":"Czarnobilska","sequence":"additional","affiliation":[{"name":"Department of Clinical and Environmental Allergology Jagiellonian University Medical College  Krakow Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wojciech","family":"Dyga","sequence":"additional","affiliation":[{"name":"Department of Clinical and Environmental Allergology Jagiellonian University Medical College  Krakow Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanja Popovi\u0107","family":"Grle","sequence":"additional","affiliation":[{"name":"Clinic for Respiratory Diseases Jordanovac University Hospital Centre Zagreb  Zagreb Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miroslav","family":"Samarzija","sequence":"additional","affiliation":[{"name":"Clinic for Respiratory Diseases Jordanovac University Hospital Centre Zagreb  Zagreb Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5489-2070","authenticated-orcid":false,"given":"Lisa","family":"Arzt\u2010Gradwohl","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venerology Medical University of Graz  Graz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Urban","family":"\u010cerpes","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venerology Medical University of Graz  Graz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6146-0188","authenticated-orcid":false,"given":"Grzegorz","family":"Porebski","sequence":"additional","affiliation":[{"name":"Department of Clinical and Environmental Allergology Jagiellonian University Medical College  Krakow Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Branko","family":"Pevec","sequence":"additional","affiliation":[{"name":"Clinic for Respiratory Diseases Jordanovac University Hospital Centre Zagreb  Zagreb Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Schadelbauer","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venerology Medical University of Graz  Graz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Kopa\u010d","sequence":"additional","affiliation":[{"name":"University Clinic of Respiratory and Allergic Diseases  Golnik Slovenia"},{"name":"Medical Faculty University of Ljubljana  Ljubljana Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julij","family":"\u0160elb","sequence":"additional","affiliation":[{"name":"University Clinic of Respiratory and Allergic Diseases  Golnik Slovenia"},{"name":"Medical Faculty University of Ljubljana  Ljubljana Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2596-4952","authenticated-orcid":false,"given":"Matija","family":"Rijavec","sequence":"additional","affiliation":[{"name":"University Clinic of Respiratory and Allergic Diseases  Golnik Slovenia"},{"name":"Biotechnical Faculty University of Ljubljana  Ljubljana Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,3,13]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2133.1999.03214.x"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)03647-3"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2222.2003.01755.x"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2009.08.027"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2020.06.008"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2023.04.016"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2021.04.045"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2010.08.035"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-021-01406-y"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2008.11.018"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2012.02809.x"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2014.11.035"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11882-015-0582-5"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2021.02.043"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2020.06.035"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.JACI.2022.11.017"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20190701"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3696"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2005.00963.x"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.24382"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2007.01569.x"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.12916"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2012.10.015"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13246380"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2021.04.013"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2010.10.004"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.23672"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2017.277897"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2022.03.007"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2016.10.031"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.13262"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(77)91953-5"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.1996.tb04632.x"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2013.10.046"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.iac.2006.05.010"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2019.07.037"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.14165"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020006157"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.JACI.2022.09.038"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2013.11.039"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-018-0506-y"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2020.05.057"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2020.11.017"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1097\/HS9.0000000000000646"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-022-01613-1"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2022.05.003"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1159\/000329856"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathmechdis-031521-042618"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.183.6.2681"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V89.9.3136"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2021.12.587"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0091-6749(97)70314-2"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2017.03.019"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2017.11.025"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.13980"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2023.07.014"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.15911"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2021.04.004"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2022007936"}],"container-title":["Allergy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/all.16084","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T05:37:44Z","timestamp":1758087464000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/all.16084"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,13]]},"references-count":59,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2024,9]]}},"alternative-id":["10.1111\/all.16084"],"URL":"https:\/\/doi.org\/10.1111\/all.16084","archive":["Portico"],"relation":{},"ISSN":["0105-4538","1398-9995"],"issn-type":[{"value":"0105-4538","type":"print"},{"value":"1398-9995","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,13]]},"assertion":[{"value":"2023-11-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}