20.500.12556/DiRROS-21514 Blood transcriptomics identifies multiple gene expression pathways associated with the clinical efficacy of Hymenoptera venom immunotherapy Allergen-specific venom immunotherapy (VIT) is a well-established therapy for Hymenoptera venom allergy (HVA). However, the precise mechanism underlying its clinical effect remains uncertain. Our study aimed to identify the molecular mechanisms associated with VIT efficiency. We prospectively included 19 patients with HVA undergoing VIT (sampled before the beginning of VIT, after reaching the maintenance dose, one year after finishing VIT, and after a sting challenge) and 9 healthy controls. RNA sequencing of whole blood was performed on an Illumina sequencing platform. Longitudinal transcriptomic profiling revealed the importance of the inhibition of the NFκB pathway and the downregulation of DUX4 transcripts for the early protection and induction of tolerance after finishing VIT. Furthermore, successful treatment was associated with inhibiting Th2, Th17, and macrophage alternative signalling pathways in synergy with the inhibition of the PPAR pathway and further silencing of the Th2 response. The immune system became activated when reaching the maintenance dose and was suppressed after finishing VIT. Finally, successful VIT restores the immune system’s balance to a state similar to that of healthy individuals. Our results underline the important role of the inhibition of four pathways in the clinical effect of VIT: Th2, Th17, NFκB, and macrophage signalling. Two biomarkers specific for successful VIT, regardless of the time of sampling, were C4BPA and RPS10-NUDT3 and should be further tested as potential biomarkers. Hymenoptera venom immunotherapy longitudinal transcriptomic profiling tolerance induction successful venom immunotherapy medicina imunoterapija strupi kožekrilcev true false true MDPI International journal of molecular sciences Angleški jezik Slovenski jezik © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Neznano 2025-02-19 08:31:52 2025-02-19 08:31:52 2025-06-03 12:43:46 0000-00-00 00:00:00 2024 0 Basel 0 Soavtorji: Peter Korošec , Mitja Košnik, Mihaela Zidarn in Matija Rijavec ; Nasl. z nasl. zaslona; Opis vira z dne 26. 3. 2024; str. 1-19 iss. 6, [article no.] 3499 Vol. 25 2024 0000-00-00 Zaloznikova Objavljeno apc 2024-01-29 2024-03-13 2024-03-20 616-097 1422-0067 10.3390/ijms25063499 190409987 https://www.mdpi.com/1422-0067/25/6/3499 1 97e89e55-ee93-11ef-9f1e-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=30742 RAZ_Demsar_Luzar_Ajda_2024.pdf RAZ_Demsar_Luzar_Ajda_2024.pdf 1 45EC9328256111637FC1E553834F007E 2c2c488f2ce77be6723630e67a06c9999fc638ec78af3c1486bc95200ac83d38 cccc7832-ee97-11ef-9f1e-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=30743 Univerzitetna klinika za pljučne bolezni in alergijo Golnik 0 0 0