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) w...
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| Veröffentlicht in: | Allergy (Copenhagen) 2024-09, Vol.79 (9), p.2458-2469 |
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| creator | Korošec, Peter Sturm, Gunter J. Lyons, Jonathan J. Marolt, Tinkara Pirc Svetina, Manca Košnik, Mitja Zidarn, Mihaela Kačar, Mark Frelih, Nina Lalek, Nika Luzar, Ajda Demšar Zver, Samo Škerget, Matevž Czarnobilska, Ewa Dyga, Wojciech Grle, Sanja Popović Samarzija, Miroslav Arzt‐Gradwohl, Lisa Čerpes, Urban Porebski, Grzegorz Pevec, Branko Schadelbauer, Eva Kopač, Peter Šelb, Julij Rijavec, Matija |
| description | 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 |
| doi_str_mv | 10.1111/all.16084 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2956683046</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2956683046</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3884-8d21bab8fd62e1a7ec487d74bd9cc7ecff10b5d345ae8ed35b492ca57b8efb393</originalsourceid><addsrcrecordid>eNp1kUFu1DAUhi1ERaeFBRdAltjAIq0T24m9rCpgkEZiU9aWHb8wrmI72AlVNhVH4CpchENwkrqdwgIJb-wnf_qk9_8IvazJWV3OuR7Hs7olgj1Bm5pKUUkp-VO0ITXhFeNUHKOTnK8JIV0jyTN0TAXrOk6aDbrdui97bJZkIeA44H6MQY_Y6zzjHsYRW5dj-UwZ62DxHhJYN-u04l8_f3__Mad1mnUG7zR2AU96dhDmjG_2EQcAi7erhxCnGZLG38rLY-f9EuJcTHpan6OjQY8ZXjzep-jz-3dXl9tq9-nDx8uLXdVTIVglbFMbbcRg2wZq3UHPRGc7Zqzs-zINQ00Mt5RxDQIs5YbJpte8MwIGQyU9RW8O3inFrwvkWXmX7_fTAeKSVSN52wpKWFvQ1_-g13FJJZSsKJGy45Q_CN8eqD7FnBMMakrOl1xUTdR9KaqUoh5KKeyrR-NiPNi_5J8WCnB-AG7cCOv_Tepitzso7wCmIJrJ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3099753539</pqid></control><display><type>article</type><title>High burden of clonal mast cell disorders and hereditary α‐tryptasemia in patients who need Hymenoptera venom immunotherapy</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Korošec, Peter ; Sturm, Gunter J. ; Lyons, Jonathan J. ; Marolt, Tinkara Pirc ; Svetina, Manca ; Košnik, Mitja ; Zidarn, Mihaela ; Kačar, Mark ; Frelih, Nina ; Lalek, Nika ; Luzar, Ajda Demšar ; Zver, Samo ; Škerget, Matevž ; Czarnobilska, Ewa ; Dyga, Wojciech ; Grle, Sanja Popović ; Samarzija, Miroslav ; Arzt‐Gradwohl, Lisa ; Čerpes, Urban ; Porebski, Grzegorz ; Pevec, Branko ; Schadelbauer, Eva ; Kopač, Peter ; Šelb, Julij ; Rijavec, Matija</creator><creatorcontrib>Korošec, Peter ; Sturm, Gunter J. ; Lyons, Jonathan J. ; Marolt, Tinkara Pirc ; Svetina, Manca ; Košnik, Mitja ; Zidarn, Mihaela ; Kačar, Mark ; Frelih, Nina ; Lalek, Nika ; Luzar, Ajda Demšar ; Zver, Samo ; Škerget, Matevž ; Czarnobilska, Ewa ; Dyga, Wojciech ; Grle, Sanja Popović ; Samarzija, Miroslav ; Arzt‐Gradwohl, Lisa ; Čerpes, Urban ; Porebski, Grzegorz ; Pevec, Branko ; Schadelbauer, Eva ; Kopač, Peter ; Šelb, Julij ; Rijavec, Matija</creatorcontrib><description>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.
In this multicenter study, we have demonstrated that clonal mast cell disease and HαT are more prevalent among individuals who need VIT; one or both was found in 27% of individuals overall. Both diagnoses were highly concentrated among individuals with severe anaphylaxis. Higher KIT p.D816V allelic burden was associated with more severe reactions. Abbreviations: BMM, bone marrow mastocytosis; BST, basal serum tryptase; HαT, hereditary alpha tryptasemia; ISM, indolent systemic mastocytosis; MMAS, monoclonal mast cell activation syndrome; PBL, peripheral blood leukocytes; VIT, venom immunotherapy.</description><identifier>ISSN: 0105-4538</identifier><identifier>ISSN: 1398-9995</identifier><identifier>EISSN: 1398-9995</identifier><identifier>DOI: 10.1111/all.16084</identifier><identifier>PMID: 38477502</identifier><language>eng</language><publisher>Denmark: Blackwell Publishing Ltd</publisher><subject>Adolescent ; Adult ; Aged ; anaphylaxis ; Animals ; Arthropod Venoms - immunology ; Asymptomatic ; Biopsy ; Child ; Child, Preschool ; Desensitization, Immunologic - methods ; Female ; Genotype ; Genotyping ; hereditary α‐tryptasemia ; Humans ; Hymenoptera ; Hymenoptera - immunology ; hypersensitivity ; Hypersensitivity - diagnosis ; Hypersensitivity - therapy ; Immunotherapy ; Insect Bites and Stings - immunology ; Insect Bites and Stings - therapy ; Leukocytes ; Male ; mast cell ; Mast Cells - immunology ; Mastocytosis ; Mastocytosis - diagnosis ; Mastocytosis - genetics ; Mastocytosis - therapy ; Middle Aged ; Peripheral blood ; Proto-Oncogene Proteins c-kit - genetics ; Sensitivity analysis ; Tryptase ; Tryptases - blood ; Venom ; Young Adult</subject><ispartof>Allergy (Copenhagen), 2024-09, Vol.79 (9), p.2458-2469</ispartof><rights>2024 The Authors. published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.</rights><rights>2024 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.</rights><rights>2024. This article is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3884-8d21bab8fd62e1a7ec487d74bd9cc7ecff10b5d345ae8ed35b492ca57b8efb393</citedby><cites>FETCH-LOGICAL-c3884-8d21bab8fd62e1a7ec487d74bd9cc7ecff10b5d345ae8ed35b492ca57b8efb393</cites><orcidid>0000-0002-2596-4952 ; 0000-0002-5489-2070 ; 0000-0002-0835-1599 ; 0000-0002-6146-0188 ; 0000-0002-4701-7374 ; 0000-0002-7245-121X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fall.16084$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fall.16084$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38477502$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Korošec, Peter</creatorcontrib><creatorcontrib>Sturm, Gunter J.</creatorcontrib><creatorcontrib>Lyons, Jonathan J.</creatorcontrib><creatorcontrib>Marolt, Tinkara Pirc</creatorcontrib><creatorcontrib>Svetina, Manca</creatorcontrib><creatorcontrib>Košnik, Mitja</creatorcontrib><creatorcontrib>Zidarn, Mihaela</creatorcontrib><creatorcontrib>Kačar, Mark</creatorcontrib><creatorcontrib>Frelih, Nina</creatorcontrib><creatorcontrib>Lalek, Nika</creatorcontrib><creatorcontrib>Luzar, Ajda Demšar</creatorcontrib><creatorcontrib>Zver, Samo</creatorcontrib><creatorcontrib>Škerget, Matevž</creatorcontrib><creatorcontrib>Czarnobilska, Ewa</creatorcontrib><creatorcontrib>Dyga, Wojciech</creatorcontrib><creatorcontrib>Grle, Sanja Popović</creatorcontrib><creatorcontrib>Samarzija, Miroslav</creatorcontrib><creatorcontrib>Arzt‐Gradwohl, Lisa</creatorcontrib><creatorcontrib>Čerpes, Urban</creatorcontrib><creatorcontrib>Porebski, Grzegorz</creatorcontrib><creatorcontrib>Pevec, Branko</creatorcontrib><creatorcontrib>Schadelbauer, Eva</creatorcontrib><creatorcontrib>Kopač, Peter</creatorcontrib><creatorcontrib>Šelb, Julij</creatorcontrib><creatorcontrib>Rijavec, Matija</creatorcontrib><title>High burden of clonal mast cell disorders and hereditary α‐tryptasemia in patients who need Hymenoptera venom immunotherapy</title><title>Allergy (Copenhagen)</title><addtitle>Allergy</addtitle><description>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.
In this multicenter study, we have demonstrated that clonal mast cell disease and HαT are more prevalent among individuals who need VIT; one or both was found in 27% of individuals overall. Both diagnoses were highly concentrated among individuals with severe anaphylaxis. Higher KIT p.D816V allelic burden was associated with more severe reactions. Abbreviations: BMM, bone marrow mastocytosis; BST, basal serum tryptase; HαT, hereditary alpha tryptasemia; ISM, indolent systemic mastocytosis; MMAS, monoclonal mast cell activation syndrome; PBL, peripheral blood leukocytes; VIT, venom immunotherapy.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>anaphylaxis</subject><subject>Animals</subject><subject>Arthropod Venoms - immunology</subject><subject>Asymptomatic</subject><subject>Biopsy</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Desensitization, Immunologic - methods</subject><subject>Female</subject><subject>Genotype</subject><subject>Genotyping</subject><subject>hereditary α‐tryptasemia</subject><subject>Humans</subject><subject>Hymenoptera</subject><subject>Hymenoptera - immunology</subject><subject>hypersensitivity</subject><subject>Hypersensitivity - diagnosis</subject><subject>Hypersensitivity - therapy</subject><subject>Immunotherapy</subject><subject>Insect Bites and Stings - immunology</subject><subject>Insect Bites and Stings - therapy</subject><subject>Leukocytes</subject><subject>Male</subject><subject>mast cell</subject><subject>Mast Cells - immunology</subject><subject>Mastocytosis</subject><subject>Mastocytosis - diagnosis</subject><subject>Mastocytosis - genetics</subject><subject>Mastocytosis - therapy</subject><subject>Middle Aged</subject><subject>Peripheral blood</subject><subject>Proto-Oncogene Proteins c-kit - genetics</subject><subject>Sensitivity analysis</subject><subject>Tryptase</subject><subject>Tryptases - blood</subject><subject>Venom</subject><subject>Young Adult</subject><issn>0105-4538</issn><issn>1398-9995</issn><issn>1398-9995</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><recordid>eNp1kUFu1DAUhi1ERaeFBRdAltjAIq0T24m9rCpgkEZiU9aWHb8wrmI72AlVNhVH4CpchENwkrqdwgIJb-wnf_qk9_8IvazJWV3OuR7Hs7olgj1Bm5pKUUkp-VO0ITXhFeNUHKOTnK8JIV0jyTN0TAXrOk6aDbrdui97bJZkIeA44H6MQY_Y6zzjHsYRW5dj-UwZ62DxHhJYN-u04l8_f3__Mad1mnUG7zR2AU96dhDmjG_2EQcAi7erhxCnGZLG38rLY-f9EuJcTHpan6OjQY8ZXjzep-jz-3dXl9tq9-nDx8uLXdVTIVglbFMbbcRg2wZq3UHPRGc7Zqzs-zINQ00Mt5RxDQIs5YbJpte8MwIGQyU9RW8O3inFrwvkWXmX7_fTAeKSVSN52wpKWFvQ1_-g13FJJZSsKJGy45Q_CN8eqD7FnBMMakrOl1xUTdR9KaqUoh5KKeyrR-NiPNi_5J8WCnB-AG7cCOv_Tepitzso7wCmIJrJ</recordid><startdate>202409</startdate><enddate>202409</enddate><creator>Korošec, Peter</creator><creator>Sturm, Gunter J.</creator><creator>Lyons, Jonathan J.</creator><creator>Marolt, Tinkara Pirc</creator><creator>Svetina, Manca</creator><creator>Košnik, Mitja</creator><creator>Zidarn, Mihaela</creator><creator>Kačar, Mark</creator><creator>Frelih, Nina</creator><creator>Lalek, Nika</creator><creator>Luzar, Ajda Demšar</creator><creator>Zver, Samo</creator><creator>Škerget, Matevž</creator><creator>Czarnobilska, Ewa</creator><creator>Dyga, Wojciech</creator><creator>Grle, Sanja Popović</creator><creator>Samarzija, Miroslav</creator><creator>Arzt‐Gradwohl, Lisa</creator><creator>Čerpes, Urban</creator><creator>Porebski, Grzegorz</creator><creator>Pevec, Branko</creator><creator>Schadelbauer, Eva</creator><creator>Kopač, Peter</creator><creator>Šelb, Julij</creator><creator>Rijavec, Matija</creator><general>Blackwell Publishing Ltd</general><scope>24P</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-2596-4952</orcidid><orcidid>https://orcid.org/0000-0002-5489-2070</orcidid><orcidid>https://orcid.org/0000-0002-0835-1599</orcidid><orcidid>https://orcid.org/0000-0002-6146-0188</orcidid><orcidid>https://orcid.org/0000-0002-4701-7374</orcidid><orcidid>https://orcid.org/0000-0002-7245-121X</orcidid></search><sort><creationdate>202409</creationdate><title>High burden of clonal mast cell disorders and hereditary α‐tryptasemia in patients who need Hymenoptera venom immunotherapy</title><author>Korošec, Peter ; Sturm, Gunter J. ; Lyons, Jonathan J. ; Marolt, Tinkara Pirc ; Svetina, Manca ; Košnik, Mitja ; Zidarn, Mihaela ; Kačar, Mark ; Frelih, Nina ; Lalek, Nika ; Luzar, Ajda Demšar ; Zver, Samo ; Škerget, Matevž ; Czarnobilska, Ewa ; Dyga, Wojciech ; Grle, Sanja Popović ; Samarzija, Miroslav ; Arzt‐Gradwohl, Lisa ; Čerpes, Urban ; Porebski, Grzegorz ; Pevec, Branko ; Schadelbauer, Eva ; Kopač, Peter ; Šelb, Julij ; Rijavec, Matija</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3884-8d21bab8fd62e1a7ec487d74bd9cc7ecff10b5d345ae8ed35b492ca57b8efb393</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>anaphylaxis</topic><topic>Animals</topic><topic>Arthropod Venoms - immunology</topic><topic>Asymptomatic</topic><topic>Biopsy</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Desensitization, Immunologic - methods</topic><topic>Female</topic><topic>Genotype</topic><topic>Genotyping</topic><topic>hereditary α‐tryptasemia</topic><topic>Humans</topic><topic>Hymenoptera</topic><topic>Hymenoptera - immunology</topic><topic>hypersensitivity</topic><topic>Hypersensitivity - diagnosis</topic><topic>Hypersensitivity - therapy</topic><topic>Immunotherapy</topic><topic>Insect Bites and Stings - immunology</topic><topic>Insect Bites and Stings - therapy</topic><topic>Leukocytes</topic><topic>Male</topic><topic>mast cell</topic><topic>Mast Cells - immunology</topic><topic>Mastocytosis</topic><topic>Mastocytosis - diagnosis</topic><topic>Mastocytosis - genetics</topic><topic>Mastocytosis - therapy</topic><topic>Middle Aged</topic><topic>Peripheral blood</topic><topic>Proto-Oncogene Proteins c-kit - genetics</topic><topic>Sensitivity analysis</topic><topic>Tryptase</topic><topic>Tryptases - blood</topic><topic>Venom</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Korošec, Peter</creatorcontrib><creatorcontrib>Sturm, Gunter J.</creatorcontrib><creatorcontrib>Lyons, Jonathan J.</creatorcontrib><creatorcontrib>Marolt, Tinkara Pirc</creatorcontrib><creatorcontrib>Svetina, Manca</creatorcontrib><creatorcontrib>Košnik, Mitja</creatorcontrib><creatorcontrib>Zidarn, Mihaela</creatorcontrib><creatorcontrib>Kačar, Mark</creatorcontrib><creatorcontrib>Frelih, Nina</creatorcontrib><creatorcontrib>Lalek, Nika</creatorcontrib><creatorcontrib>Luzar, Ajda Demšar</creatorcontrib><creatorcontrib>Zver, Samo</creatorcontrib><creatorcontrib>Škerget, Matevž</creatorcontrib><creatorcontrib>Czarnobilska, Ewa</creatorcontrib><creatorcontrib>Dyga, Wojciech</creatorcontrib><creatorcontrib>Grle, Sanja Popović</creatorcontrib><creatorcontrib>Samarzija, Miroslav</creatorcontrib><creatorcontrib>Arzt‐Gradwohl, Lisa</creatorcontrib><creatorcontrib>Čerpes, Urban</creatorcontrib><creatorcontrib>Porebski, Grzegorz</creatorcontrib><creatorcontrib>Pevec, Branko</creatorcontrib><creatorcontrib>Schadelbauer, Eva</creatorcontrib><creatorcontrib>Kopač, Peter</creatorcontrib><creatorcontrib>Šelb, Julij</creatorcontrib><creatorcontrib>Rijavec, Matija</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Allergy (Copenhagen)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Korošec, Peter</au><au>Sturm, Gunter J.</au><au>Lyons, Jonathan J.</au><au>Marolt, Tinkara Pirc</au><au>Svetina, Manca</au><au>Košnik, Mitja</au><au>Zidarn, Mihaela</au><au>Kačar, Mark</au><au>Frelih, Nina</au><au>Lalek, Nika</au><au>Luzar, Ajda Demšar</au><au>Zver, Samo</au><au>Škerget, Matevž</au><au>Czarnobilska, Ewa</au><au>Dyga, Wojciech</au><au>Grle, Sanja Popović</au><au>Samarzija, Miroslav</au><au>Arzt‐Gradwohl, Lisa</au><au>Čerpes, Urban</au><au>Porebski, Grzegorz</au><au>Pevec, Branko</au><au>Schadelbauer, Eva</au><au>Kopač, Peter</au><au>Šelb, Julij</au><au>Rijavec, Matija</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>High burden of clonal mast cell disorders and hereditary α‐tryptasemia in patients who need Hymenoptera venom immunotherapy</atitle><jtitle>Allergy (Copenhagen)</jtitle><addtitle>Allergy</addtitle><date>2024-09</date><risdate>2024</risdate><volume>79</volume><issue>9</issue><spage>2458</spage><epage>2469</epage><pages>2458-2469</pages><issn>0105-4538</issn><issn>1398-9995</issn><eissn>1398-9995</eissn><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.
In this multicenter study, we have demonstrated that clonal mast cell disease and HαT are more prevalent among individuals who need VIT; one or both was found in 27% of individuals overall. Both diagnoses were highly concentrated among individuals with severe anaphylaxis. Higher KIT p.D816V allelic burden was associated with more severe reactions. Abbreviations: BMM, bone marrow mastocytosis; BST, basal serum tryptase; HαT, hereditary alpha tryptasemia; ISM, indolent systemic mastocytosis; MMAS, monoclonal mast cell activation syndrome; PBL, peripheral blood leukocytes; VIT, venom immunotherapy.</abstract><cop>Denmark</cop><pub>Blackwell Publishing Ltd</pub><pmid>38477502</pmid><doi>10.1111/all.16084</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-2596-4952</orcidid><orcidid>https://orcid.org/0000-0002-5489-2070</orcidid><orcidid>https://orcid.org/0000-0002-0835-1599</orcidid><orcidid>https://orcid.org/0000-0002-6146-0188</orcidid><orcidid>https://orcid.org/0000-0002-4701-7374</orcidid><orcidid>https://orcid.org/0000-0002-7245-121X</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0105-4538 |
| ispartof | Allergy (Copenhagen), 2024-09, Vol.79 (9), p.2458-2469 |
| issn | 0105-4538 1398-9995 1398-9995 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2956683046 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Adolescent Adult Aged anaphylaxis Animals Arthropod Venoms - immunology Asymptomatic Biopsy Child Child, Preschool Desensitization, Immunologic - methods Female Genotype Genotyping hereditary α‐tryptasemia Humans Hymenoptera Hymenoptera - immunology hypersensitivity Hypersensitivity - diagnosis Hypersensitivity - therapy Immunotherapy Insect Bites and Stings - immunology Insect Bites and Stings - therapy Leukocytes Male mast cell Mast Cells - immunology Mastocytosis Mastocytosis - diagnosis Mastocytosis - genetics Mastocytosis - therapy Middle Aged Peripheral blood Proto-Oncogene Proteins c-kit - genetics Sensitivity analysis Tryptase Tryptases - blood Venom Young Adult |
| title | High burden of clonal mast cell disorders and hereditary α‐tryptasemia in patients who need Hymenoptera venom immunotherapy |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-09T00%3A34%3A31IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=High%20burden%20of%20clonal%20mast%20cell%20disorders%20and%20hereditary%20%CE%B1%E2%80%90tryptasemia%20in%20patients%20who%20need%20Hymenoptera%20venom%20immunotherapy&rft.jtitle=Allergy%20(Copenhagen)&rft.au=Koro%C5%A1ec,%20Peter&rft.date=2024-09&rft.volume=79&rft.issue=9&rft.spage=2458&rft.epage=2469&rft.pages=2458-2469&rft.issn=0105-4538&rft.eissn=1398-9995&rft_id=info:doi/10.1111/all.16084&rft_dat=%3Cproquest_cross%3E2956683046%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=3099753539&rft_id=info:pmid/38477502&rfr_iscdi=true |