Blood transcriptomics identifies multiple gene expression pathways associated with the clinical efficacy of Hymenoptera venom immunotherapy

Demšar Luzar, Ajda (author), Korošec, Peter (author), Košnik, Mitja (author), Zidarn, Mihaela (author), Rijavec, Matija (author)

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.

• Language: English
• Keywords: Hymenoptera venom immunotherapy, longitudinal transcriptomic profiling, tolerance induction, successful venom immunotherapy
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: BF - Biotechnical Faculty; FFA - Faculty of Pharmacy; MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2024
• Number of pages: 19 str.
• Numbering: Vol. 25, iss. 6, art. 3499
• PID: 20.500.12556/RUL-164950
• UDC: 616-097
• ISSN on article: 1422-0067
• DOI: 10.3390/ijms25063499
• COBISS.SI-ID: 190409987
• Publication date in RUL: 19.11.2024

Record is a part of a journal

• Title: International journal of molecular sciences
• Shortened title: Int. j. mol. sci.
• Publisher: MDPI
• ISSN: 1422-0067
• COBISS.SI-ID: 2779162

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: medicina, imunoterapija, strupi kožekrilcev

Projects

• Funder: ARIS - Slovenian Research and Innovation Agency
• Project number: P3-0360
• Name: Celostna obravnava alergijskih bolezni in astme v Sloveniji: od epidemiologije do genetike

• Funder: ARIS - Slovenian Research and Innovation Agency
• Funding programme: Young researchers