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

Feng Hefeng, Dimitrii Pogorelov, Sebastian Bode, Xin He, Javier Ramiro-Garcia, Fanny Hedin, Wim Ammerlaan, Maria Konstantinou, Christophe Capelle, Ni Zeng, Aurélie Poli, Olivia Domingues, Guillem Montamat, Oliver Hunewald, Séverine Cire, Alexandre Baron, Joseph Longworth, Lorie Neuberger-Castillo, Dominique Revets, Léa GuyonnetAgnieszka Demczuk, Sylvie Delhalle, Jacques Zimmer, Vladimir Benes, Françoise Codreanu-Morel, Christiane Lehners-Weber, Ilse Weets, Pinar Alper, Dirk Brenner, Jan Gutermuth, Coralie Guérin, Martine Morisset, François Hentges, Reinhard Schneider, Mohamed Shamji, Fay Betsou, Paul Wilmes, Enrico Glaab, Jorge Goncalves, Antonio Cosma, Markus Ollert

Research output: Working paperPreprint


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. Here we applied a multilayer-omics approach to reveal dynamic peripheral immune landscapes during AIT-initiation phase in venom allergy patients (VAP) versus pollen-allergic and healthy controls. Already at baseline, VAP exhibited altered abundances of several cell types, including antigen-presenting cells (APC) and hybrid types, especially pDC-mDC hybrids. At 8-24h following AIT launch in VAP, we identified 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 occurred. A disequilibrium between serum IL-6 and APC in VAP baseline was restored at day seven following AIT launch. Our longitudinal analysis discovers molecular switches during initiation-phase insect-venom AIT that secure long-term outcomes.
Original languageEnglish
Publication statusPublished - 22 Feb 2024

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