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

26 nov. 2024Nature Communications

DOI : 10.1038/s41467-024-54684-2

Auteurs

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

Résumé

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.

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