Multiomics approaches disclose very-early molecular and cellular switches during insect-venom allergen-specific immunotherapy: an observational study
Abstract Allergen-specific immunotherapy (AIT) induces immune tolerance, showing the highest success rate (>95%) for insect venom while a much lower chance for pollen allergy. However, the molecular switches leading to successful durable tolerance restoration remain elusive. The primary outcome o...
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2024-11-01
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| author | Dimitrii Pogorelov Sebastian Felix Nepomuk Bode Xin He Javier Ramiro-Garcia Fanny Hedin Wim Ammerlaan Maria Konstantinou Christophe M. Capelle Ni Zeng Aurélie Poli Olivia Domingues Guillem Montamat Oliver Hunewald Séverine Ciré Alexandre Baron Joseph Longworth Agnieszka Demczuk Murilo Luiz Bazon Ingrid Casper Ludger Klimek Lorie Neuberger-Castillo Dominique Revets Lea Guyonnet Sylvie Delhalle Jacques Zimmer Vladimir Benes Françoise Codreanu-Morel Christiane Lehners-Weber Ilse Weets Pinar Alper Dirk Brenner Jan Gutermuth Coralie Guerin Martine Morisset François Hentges Reinhard Schneider Mohamed H. Shamji Fay Betsou Paul Wilmes Enrico Glaab Antonio Cosma Jorge Goncalves Feng Q. Hefeng Markus Ollert |
| author_facet | Dimitrii Pogorelov Sebastian Felix Nepomuk Bode Xin He Javier Ramiro-Garcia Fanny Hedin Wim Ammerlaan Maria Konstantinou Christophe M. Capelle Ni Zeng Aurélie Poli Olivia Domingues Guillem Montamat Oliver Hunewald Séverine Ciré Alexandre Baron Joseph Longworth Agnieszka Demczuk Murilo Luiz Bazon Ingrid Casper Ludger Klimek Lorie Neuberger-Castillo Dominique Revets Lea Guyonnet Sylvie Delhalle Jacques Zimmer Vladimir Benes Françoise Codreanu-Morel Christiane Lehners-Weber Ilse Weets Pinar Alper Dirk Brenner Jan Gutermuth Coralie Guerin Martine Morisset François Hentges Reinhard Schneider Mohamed H. Shamji Fay Betsou Paul Wilmes Enrico Glaab Antonio Cosma Jorge Goncalves Feng Q. Hefeng Markus Ollert |
| author_sort | Dimitrii Pogorelov |
| collection | DOAJ |
| description | Abstract Allergen-specific immunotherapy (AIT) induces immune tolerance, showing the highest success rate (>95%) for insect venom while a much lower chance for pollen allergy. However, the molecular switches leading to successful durable tolerance restoration remain elusive. The primary outcome of this observational study is the comprehensive immunological cellular characterization during the AIT initiation phase, whereas the secondary outcomes are the serological and Th2-cell-type-specific transcriptomic analyses. Here we apply a multilayer-omics approach to reveal dynamic peripheral immune landscapes during the AIT-initiation phase in venom allergy patients (VAP) versus pollen-allergic and healthy controls. Already at baseline, VAP exhibit altered abundances of several cell types, including classical monocytes (cMono), CD4+ hybrid type 1-type 17 cells (Th1-Th17 or Th1/17) and CD8+ counterparts (Tc1-Tc17 or Tc1/17). At 8-24 h following AIT launch in VAP, we identify a uniform AIT-elicited pulse of late-transitional/IL-10-producing B cells, IL-6 signaling within Th2 cells and non-inflammatory serum-IL-6 levels. Sequential induction of activation and survival protein markers also immediately occur. A disequilibrium between serum IL-6 and cMono in VAP baseline is restored at day seven following AIT launch. Our longitudinal analysis discovers molecular switches during initiation-phase insect-venom AIT that secure long-term outcomes. Trial number: NCT02931955. |
| format | Article |
| id | doaj-art-4241e882ff6348d9b88a6e9c30ce2b6f |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
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| series | Nature Communications |
| spelling | doaj-art-4241e882ff6348d9b88a6e9c30ce2b6f2025-08-20T02:49:17ZengNature PortfolioNature Communications2041-17232024-11-0115112210.1038/s41467-024-54684-2Multiomics approaches disclose very-early molecular and cellular switches during insect-venom allergen-specific immunotherapy: an observational studyDimitrii Pogorelov0Sebastian Felix Nepomuk Bode1Xin He2Javier Ramiro-Garcia3Fanny Hedin4Wim Ammerlaan5Maria Konstantinou6Christophe M. Capelle7Ni Zeng8Aurélie Poli9Olivia Domingues10Guillem Montamat11Oliver Hunewald12Séverine Ciré13Alexandre Baron14Joseph Longworth15Agnieszka Demczuk16Murilo Luiz Bazon17Ingrid Casper18Ludger Klimek19Lorie Neuberger-Castillo20Dominique Revets21Lea Guyonnet22Sylvie Delhalle23Jacques Zimmer24Vladimir Benes25Françoise Codreanu-Morel26Christiane Lehners-Weber27Ilse Weets28Pinar Alper29Dirk Brenner30Jan Gutermuth31Coralie Guerin32Martine Morisset33François Hentges34Reinhard Schneider35Mohamed H. Shamji36Fay Betsou37Paul Wilmes38Enrico Glaab39Antonio Cosma40Jorge Goncalves41Feng Q. Hefeng42Markus Ollert43Department of Infection and Immunity, Luxembourg Institute of Health (LIH)Department of Infection and Immunity, Luxembourg Institute of Health (LIH)Luxembourg Centre for Systems Biomedicine, University of LuxembourgLuxembourg Centre for Systems Biomedicine, University of LuxembourgNational Cytometry Platform, Luxembourg Institute of HealthIntegrated BioBank of Luxembourg, Luxembourg Institute of HealthNational Cytometry Platform, Luxembourg Institute of HealthDepartment of Infection and Immunity, Luxembourg Institute of Health (LIH)Department of Infection and Immunity, Luxembourg Institute of Health (LIH)Department of Infection and Immunity, Luxembourg Institute of Health (LIH)Department of Infection and Immunity, Luxembourg Institute of Health (LIH)Department of Infection and Immunity, Luxembourg Institute of Health (LIH)Department of Infection and Immunity, Luxembourg Institute of Health (LIH)Department of Infection and Immunity, Luxembourg Institute of Health (LIH)Department of Infection and Immunity, Luxembourg Institute of Health (LIH)Department of Infection and Immunity, Luxembourg Institute of Health (LIH)Department of Infection and Immunity, Luxembourg Institute of Health (LIH)Department of Infection and Immunity, Luxembourg Institute of Health (LIH)Center for Rhinology and AllergologyCenter for Rhinology and AllergologyIntegrated BioBank of Luxembourg, Luxembourg Institute of HealthNational Cytometry Platform, Luxembourg Institute of HealthDepartment of Infection and Immunity, Luxembourg Institute of Health (LIH)Department of Infection and Immunity, Luxembourg Institute of Health (LIH)Department of Infection and Immunity, Luxembourg Institute of Health (LIH)Genomics Core Facility, European Molecular Biology LaboratoryNational Unit of Immunology-Allergology, Centre Hospitalier de LuxembourgNational Unit of Immunology-Allergology, Centre Hospitalier de LuxembourgDepartment of Clinical Biology/ Research Group Experimental Pharmacology, Vrije Universiteit Brussel, Universitair Ziekenhuis BrusselLuxembourg Centre for Systems Biomedicine, University of LuxembourgDepartment of Infection and Immunity, Luxembourg Institute of Health (LIH)Department of Dermatology, Vrije Universiteit Brussel, Universitair Ziekenhuis BrusselDepartment of Infection and Immunity, Luxembourg Institute of Health (LIH)National Unit of Immunology-Allergology, Centre Hospitalier de LuxembourgNational Unit of Immunology-Allergology, Centre Hospitalier de LuxembourgLuxembourg Centre for Systems Biomedicine, University of LuxembourgImmunomodulation and Tolerance Group, Allergy and Clinical Immunology, Department of National Heart and Lung Institute, Imperial College LondonIntegrated BioBank of Luxembourg, Luxembourg Institute of HealthDepartment of Life Sciences and Medicine, Faculty of Science, Technology and Medicine, University of LuxembourgLuxembourg Centre for Systems Biomedicine, University of LuxembourgNational Cytometry Platform, Luxembourg Institute of HealthLuxembourg Centre for Systems Biomedicine, University of LuxembourgDepartment of Infection and Immunity, Luxembourg Institute of Health (LIH)Department of Infection and Immunity, Luxembourg Institute of Health (LIH)Abstract Allergen-specific immunotherapy (AIT) induces immune tolerance, showing the highest success rate (>95%) for insect venom while a much lower chance for pollen allergy. However, the molecular switches leading to successful durable tolerance restoration remain elusive. The primary outcome of this observational study is the comprehensive immunological cellular characterization during the AIT initiation phase, whereas the secondary outcomes are the serological and Th2-cell-type-specific transcriptomic analyses. Here we apply a multilayer-omics approach to reveal dynamic peripheral immune landscapes during the AIT-initiation phase in venom allergy patients (VAP) versus pollen-allergic and healthy controls. Already at baseline, VAP exhibit altered abundances of several cell types, including classical monocytes (cMono), CD4+ hybrid type 1-type 17 cells (Th1-Th17 or Th1/17) and CD8+ counterparts (Tc1-Tc17 or Tc1/17). At 8-24 h following AIT launch in VAP, we identify a uniform AIT-elicited pulse of late-transitional/IL-10-producing B cells, IL-6 signaling within Th2 cells and non-inflammatory serum-IL-6 levels. Sequential induction of activation and survival protein markers also immediately occur. A disequilibrium between serum IL-6 and cMono in VAP baseline is restored at day seven following AIT launch. Our longitudinal analysis discovers molecular switches during initiation-phase insect-venom AIT that secure long-term outcomes. Trial number: NCT02931955.https://doi.org/10.1038/s41467-024-54684-2 |
| spellingShingle | Dimitrii Pogorelov Sebastian Felix Nepomuk Bode Xin He Javier Ramiro-Garcia Fanny Hedin Wim Ammerlaan Maria Konstantinou Christophe M. Capelle Ni Zeng Aurélie Poli Olivia Domingues Guillem Montamat Oliver Hunewald Séverine Ciré Alexandre Baron Joseph Longworth Agnieszka Demczuk Murilo Luiz Bazon Ingrid Casper Ludger Klimek Lorie Neuberger-Castillo Dominique Revets Lea Guyonnet Sylvie Delhalle Jacques Zimmer Vladimir Benes Françoise Codreanu-Morel Christiane Lehners-Weber Ilse Weets Pinar Alper Dirk Brenner Jan Gutermuth Coralie Guerin Martine Morisset François Hentges Reinhard Schneider Mohamed H. Shamji Fay Betsou Paul Wilmes Enrico Glaab Antonio Cosma Jorge Goncalves Feng Q. Hefeng Markus Ollert Multiomics approaches disclose very-early molecular and cellular switches during insect-venom allergen-specific immunotherapy: an observational study Nature Communications |
| title | Multiomics approaches disclose very-early molecular and cellular switches during insect-venom allergen-specific immunotherapy: an observational study |
| title_full | Multiomics approaches disclose very-early molecular and cellular switches during insect-venom allergen-specific immunotherapy: an observational study |
| title_fullStr | Multiomics approaches disclose very-early molecular and cellular switches during insect-venom allergen-specific immunotherapy: an observational study |
| title_full_unstemmed | Multiomics approaches disclose very-early molecular and cellular switches during insect-venom allergen-specific immunotherapy: an observational study |
| title_short | Multiomics approaches disclose very-early molecular and cellular switches during insect-venom allergen-specific immunotherapy: an observational study |
| title_sort | multiomics approaches disclose very early molecular and cellular switches during insect venom allergen specific immunotherapy an observational study |
| url | https://doi.org/10.1038/s41467-024-54684-2 |
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