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Multiomics approaches disclose very-early molecular and cellular switches during insect-venom allergen-specific immunotherapy: an observational study

Author

Listed:
  • Dimitrii Pogorelov

    (Luxembourg Institute of Health (LIH)
    University of Luxembourg
    Technical University of Munich)

  • Sebastian Felix Nepomuk Bode

    (Luxembourg Institute of Health (LIH)
    Ulm University Medical Center
    Faculty of Medicine)

  • Xin He

    (University of Luxembourg)

  • Javier Ramiro-Garcia

    (University of Luxembourg)

  • Fanny Hedin

    (Luxembourg Institute of Health)

  • Wim Ammerlaan

    (Luxembourg Institute of Health)

  • Maria Konstantinou

    (Luxembourg Institute of Health)

  • Christophe M. Capelle

    (Luxembourg Institute of Health (LIH)
    University of Luxembourg
    ETH Zurich)

  • Ni Zeng

    (Luxembourg Institute of Health (LIH)
    University of Luxembourg)

  • Aurélie Poli

    (Luxembourg Institute of Health (LIH)
    Luxembourg Institute of Health)

  • Olivia Domingues

    (Luxembourg Institute of Health (LIH))

  • Guillem Montamat

    (Luxembourg Institute of Health (LIH))

  • Oliver Hunewald

    (Luxembourg Institute of Health (LIH))

  • Séverine Ciré

    (Luxembourg Institute of Health (LIH))

  • Alexandre Baron

    (Luxembourg Institute of Health (LIH))

  • Joseph Longworth

    (Luxembourg Institute of Health (LIH)
    University of Luxembourg)

  • Agnieszka Demczuk

    (Luxembourg Institute of Health (LIH)
    University of Luxembourg)

  • Murilo Luiz Bazon

    (Luxembourg Institute of Health (LIH))

  • Ingrid Casper

    (Center for Rhinology and Allergology)

  • Ludger Klimek

    (Center for Rhinology and Allergology)

  • Lorie Neuberger-Castillo

    (Luxembourg Institute of Health)

  • Dominique Revets

    (Luxembourg Institute of Health)

  • Lea Guyonnet

    (Luxembourg Institute of Health (LIH)
    Université de Paris)

  • Sylvie Delhalle

    (Luxembourg Institute of Health (LIH))

  • Jacques Zimmer

    (Luxembourg Institute of Health (LIH))

  • Vladimir Benes

    (European Molecular Biology Laboratory)

  • Françoise Codreanu-Morel

    (Centre Hospitalier de Luxembourg)

  • Christiane Lehners-Weber

    (Centre Hospitalier de Luxembourg)

  • Ilse Weets

    (Universitair Ziekenhuis Brussel)

  • Pinar Alper

    (University of Luxembourg)

  • Dirk Brenner

    (Luxembourg Institute of Health (LIH)
    University of Luxembourg
    University of Southern Denmark)

  • Jan Gutermuth

    (Universitair Ziekenhuis Brussel)

  • Coralie Guerin

    (Luxembourg Institute of Health (LIH)
    Université de Paris)

  • Martine Morisset

    (Centre Hospitalier de Luxembourg
    Angers University Hospital)

  • François Hentges

    (Centre Hospitalier de Luxembourg)

  • Reinhard Schneider

    (University of Luxembourg)

  • Mohamed H. Shamji

    (Imperial College London)

  • Fay Betsou

    (Luxembourg Institute of Health
    Université Paris Cité)

  • Paul Wilmes

    (University of Luxembourg
    University of Luxembourg)

  • Enrico Glaab

    (University of Luxembourg)

  • Antonio Cosma

    (Luxembourg Institute of Health)

  • Jorge Goncalves

    (University of Luxembourg)

  • Feng Q. Hefeng

    (Luxembourg Institute of Health (LIH))

  • Markus Ollert

    (Luxembourg Institute of Health (LIH)
    University of Southern Denmark)

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.

Suggested Citation

  • 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, 2024. "Multiomics approaches disclose very-early molecular and cellular switches during insect-venom allergen-specific immunotherapy: an observational study," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54684-2
    DOI: 10.1038/s41467-024-54684-2
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