TY - UNPB
T1 - Multiomics approaches disclose very-early molecular and cellular switches during insect-venom allergen-specific immunotherapy
AU - Hefeng, Feng
AU - Pogorelov, Dimitrii
AU - Bode, Sebastian
AU - He, Xin
AU - Ramiro-Garcia, Javier
AU - Hedin, Fanny
AU - Ammerlaan, Wim
AU - Konstantinou, Maria
AU - Capelle, Christophe
AU - Zeng, Ni
AU - Poli, Aurélie
AU - Domingues, Olivia
AU - Montamat, Guillem
AU - Hunewald, Oliver
AU - Cire, Séverine
AU - Baron, Alexandre
AU - Longworth, Joseph
AU - Neuberger-Castillo, Lorie
AU - Revets, Dominique
AU - Guyonnet, Léa
AU - Demczuk, Agnieszka
AU - Delhalle, Sylvie
AU - Zimmer, Jacques
AU - Benes, Vladimir
AU - Codreanu-Morel, Françoise
AU - Lehners-Weber, Christiane
AU - Weets, Ilse
AU - Alper, Pinar
AU - Brenner, Dirk
AU - Gutermuth, Jan
AU - Guérin, Coralie
AU - Morisset, Martine
AU - Hentges, François
AU - Schneider, Reinhard
AU - Shamji, Mohamed
AU - Betsou, Fay
AU - Wilmes, Paul
AU - Glaab, Enrico
AU - Goncalves, Jorge
AU - Cosma, Antonio
AU - Ollert, Markus
PY - 2024/2/22
Y1 - 2024/2/22
N2 - 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.
AB - 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.
U2 - 10.21203/rs.3.rs-3917969/v1
DO - 10.21203/rs.3.rs-3917969/v1
M3 - Preprint
T3 - Research Square
BT - Multiomics approaches disclose very-early molecular and cellular switches during insect-venom allergen-specific immunotherapy
ER -