Nature Communications (Nov 2024)
Multiomics approaches disclose very-early molecular and cellular switches during insect-venom allergen-specific immunotherapy: an observational study
- 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
Affiliations
- Dimitrii Pogorelov
- Department of Infection and Immunity, Luxembourg Institute of Health (LIH)
- Sebastian Felix Nepomuk Bode
- Department of Infection and Immunity, Luxembourg Institute of Health (LIH)
- Xin He
- Luxembourg Centre for Systems Biomedicine, University of Luxembourg
- Javier Ramiro-Garcia
- Luxembourg Centre for Systems Biomedicine, University of Luxembourg
- Fanny Hedin
- National Cytometry Platform, Luxembourg Institute of Health
- Wim Ammerlaan
- Integrated BioBank of Luxembourg, Luxembourg Institute of Health
- Maria Konstantinou
- National Cytometry Platform, Luxembourg Institute of Health
- Christophe M. Capelle
- Department of Infection and Immunity, Luxembourg Institute of Health (LIH)
- Ni Zeng
- Department of Infection and Immunity, Luxembourg Institute of Health (LIH)
- Aurélie Poli
- Department of Infection and Immunity, Luxembourg Institute of Health (LIH)
- Olivia Domingues
- Department of Infection and Immunity, Luxembourg Institute of Health (LIH)
- Guillem Montamat
- Department of Infection and Immunity, Luxembourg Institute of Health (LIH)
- Oliver Hunewald
- Department of Infection and Immunity, Luxembourg Institute of Health (LIH)
- Séverine Ciré
- Department of Infection and Immunity, Luxembourg Institute of Health (LIH)
- Alexandre Baron
- Department of Infection and Immunity, Luxembourg Institute of Health (LIH)
- Joseph Longworth
- Department of Infection and Immunity, Luxembourg Institute of Health (LIH)
- Agnieszka Demczuk
- Department of Infection and Immunity, Luxembourg Institute of Health (LIH)
- Murilo Luiz Bazon
- Department of Infection and Immunity, Luxembourg Institute of Health (LIH)
- Ingrid Casper
- Center for Rhinology and Allergology
- Ludger Klimek
- Center for Rhinology and Allergology
- Lorie Neuberger-Castillo
- Integrated BioBank of Luxembourg, Luxembourg Institute of Health
- Dominique Revets
- National Cytometry Platform, Luxembourg Institute of Health
- Lea Guyonnet
- Department of Infection and Immunity, Luxembourg Institute of Health (LIH)
- Sylvie Delhalle
- Department of Infection and Immunity, Luxembourg Institute of Health (LIH)
- Jacques Zimmer
- Department of Infection and Immunity, Luxembourg Institute of Health (LIH)
- Vladimir Benes
- Genomics Core Facility, European Molecular Biology Laboratory
- Françoise Codreanu-Morel
- National Unit of Immunology-Allergology, Centre Hospitalier de Luxembourg
- Christiane Lehners-Weber
- National Unit of Immunology-Allergology, Centre Hospitalier de Luxembourg
- Ilse Weets
- Department of Clinical Biology/ Research Group Experimental Pharmacology, Vrije Universiteit Brussel, Universitair Ziekenhuis Brussel
- Pinar Alper
- Luxembourg Centre for Systems Biomedicine, University of Luxembourg
- Dirk Brenner
- Department of Infection and Immunity, Luxembourg Institute of Health (LIH)
- Jan Gutermuth
- Department of Dermatology, Vrije Universiteit Brussel, Universitair Ziekenhuis Brussel
- Coralie Guerin
- Department of Infection and Immunity, Luxembourg Institute of Health (LIH)
- Martine Morisset
- National Unit of Immunology-Allergology, Centre Hospitalier de Luxembourg
- François Hentges
- National Unit of Immunology-Allergology, Centre Hospitalier de Luxembourg
- Reinhard Schneider
- Luxembourg Centre for Systems Biomedicine, University of Luxembourg
- Mohamed H. Shamji
- Immunomodulation and Tolerance Group, Allergy and Clinical Immunology, Department of National Heart and Lung Institute, Imperial College London
- Fay Betsou
- Integrated BioBank of Luxembourg, Luxembourg Institute of Health
- Paul Wilmes
- Department of Life Sciences and Medicine, Faculty of Science, Technology and Medicine, University of Luxembourg
- Enrico Glaab
- Luxembourg Centre for Systems Biomedicine, University of Luxembourg
- Antonio Cosma
- National Cytometry Platform, Luxembourg Institute of Health
- Jorge Goncalves
- Luxembourg Centre for Systems Biomedicine, University of Luxembourg
- Feng Q. Hefeng
- Department of Infection and Immunity, Luxembourg Institute of Health (LIH)
- Markus Ollert
- Department of Infection and Immunity, Luxembourg Institute of Health (LIH)
- DOI
- https://doi.org/10.1038/s41467-024-54684-2
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 1 – 22
Abstract
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.
