Multiomics approaches disclose very-early molecular and cellular switches during insect-venom allergen-specific immunotherapy: an observational study
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<sup>+</sup> hybrid type 1-type 17 cells (Th1-Th17 or Th1/17) and CD8<sup>+</sup> 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.
Authors
- Agnieszka Demczuk (ORCID: https://orcid.org/0000-0001-9868-7653)
- Sylvie Delhalle (ORCID: https://orcid.org/0000-0002-5573-754X)
- Oliver Hunewald (ORCID: https://orcid.org/0000-0001-5402-5084)
- Jan Gutermuth (ORCID: https://orcid.org/0000-0002-9252-6004)
- Sebastian F. N. Bode (ORCID: https://orcid.org/0000-0001-7217-3312)
- Wim Ammerlaan
- Séverine Ciré (ORCID: https://orcid.org/0000-0001-9991-2170)
- Aurélie Poli (ORCID: https://orcid.org/0000-0002-7986-0761)
- Dimitrii Pogorelov
- Antonio Cosma (ORCID: https://orcid.org/0000-0002-3686-8034)
- Olivia Domingues (ORCID: https://orcid.org/0009-0005-8219-296X)
- Fanny Hedin (ORCID: https://orcid.org/0000-0002-2563-3061)
- Maria Konstantinou (ORCID: https://orcid.org/0000-0002-3727-6188)
- Markus W. Ollert (ORCID: https://orcid.org/0000-0002-8055-0103)
- Christophe Capelle (ORCID: https://orcid.org/0000-0002-9110-9583)
- Joseph Longworth (ORCID: https://orcid.org/0000-0003-4644-921X)
- Jorge Gonçalves (ORCID: https://orcid.org/0000-0002-5228-6165)
- Ludger Klimek (ORCID: https://orcid.org/0000-0002-2455-0192)
- M. Morisset (ORCID: https://orcid.org/0000-0002-4028-703X)
- Léa Guyonnet (ORCID: https://orcid.org/0000-0003-4815-1193)
- Ni Zeng (ORCID: https://orcid.org/0000-0003-2756-6074)
- Ilse Weets (ORCID: https://orcid.org/0000-0002-9007-5203)
- Lorie Neuberger-Castillo
- Jacques Zimmer (ORCID: https://orcid.org/0000-0002-7118-6944)
- Pinar Alper (ORCID: https://orcid.org/0000-0002-2224-0780)
- Vladimı́r Beneš (ORCID: https://orcid.org/0000-0002-0352-2547)
- Christiane Lehners‐Weber
- Enrico Glaab (ORCID: https://orcid.org/0000-0003-3977-7469)
- Ingrid Casper (ORCID: https://orcid.org/0000-0002-4596-8416)
- Mohamed H. Shamji (ORCID: https://orcid.org/0000-0003-3425-3463)
- Murilo Luiz Bazon (ORCID: https://orcid.org/0000-0002-1102-8661)
- Fay Betsou (ORCID: https://orcid.org/0000-0002-0558-4653)
- Guillem Montamat (ORCID: https://orcid.org/0000-0003-2922-7092)
- Feng He (ORCID: https://orcid.org/0000-0003-2657-7361)
- Alexandre Baron (ORCID: https://orcid.org/0000-0002-6907-3676)
- Françoise Codreanu‐Morel
- Dirk Brenner (ORCID: https://orcid.org/0000-0001-8979-1045)
- Coralie L. Guérin (ORCID: https://orcid.org/0000-0002-1840-4017)
- Dominique Revets
- Paul Wilmes (ORCID: https://orcid.org/0000-0002-6478-2924)
- Reinhard Schneider (ORCID: https://orcid.org/0000-0002-8278-1618)
- Javier Ramiro‐Garcia (ORCID: https://orcid.org/0000-0003-3896-3833)
- François Hentges
- He Xin (ORCID: https://orcid.org/0000-0003-2758-4360)
Institutions
- Vrije Universiteit Brussel (BE)
- Inserm (FR)
- Institut Pasteur (FR)
- University of Freiburg (DE)
- Centre Hospitalier de Luxembourg (LU)
- University of Southern Denmark (DK)
- University of Luxembourg (LU)
- Universität Ulm (DE)
- Université Paris Cité (FR)
- University Medical Center Freiburg (DE)
- ETH Zurich (CH)
- Luxembourg Institute of Health (LU)
- Zentrum für Rhinologie und Allergologie (DE)
- Universitair Ziekenhuis Brussel (BE)
- European Molecular Biology Laboratory (DE)
- Imperial College London (GB)
- Université d'Angers (FR)
- Technical University of Munich (DE)
- Institut Curie (FR)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-11-26
- DOI
- https://doi.org/10.1038/s41467-024-54684-2
- Citations
- 8
- Primary Topic
- Allergic Rhinitis and Sensitization
- Type
- article
- Field-Weighted Citation Impact
- 3.06
Funders
- Integrated BioBank of Luxembourg
- European Commission
- Fonds National de la Recherche Luxembourg
- International Council for Canadian Studies
- Action LIONS Vaincre le Cancer
- European Academy of Allergy and Clinical Immunology
- HORIZON EUROPE Framework Programme