| Title: |
Genome-Wide Blood DNA Methylation Profiling in Birch Pollen Allergic Patients Undergoing Allergen-Specific Immunotherapy |
| Authors: |
Lahnsteiner, Angelika; Ellmer, Victoria; Hao, Mengzhen; Tannert, Line Kring; Versteeg, Serge A.; Bindslev-Jensen, Carsten; van Ree, Ronald; Risch, Angela; Aglas, Lorenz |
| Source: |
Lahnsteiner, A, Ellmer, V, Hao, M, Tannert, L K, Versteeg, S A, Bindslev-Jensen, C, van Ree, R, Risch, A & Aglas, L 2025, 'Genome-Wide Blood DNA Methylation Profiling in Birch Pollen Allergic Patients Undergoing Allergen-Specific Immunotherapy', Allergy: European Journal of Allergy and Clinical Immunology, vol. 80, no. 12, pp. 3412-3423. https://doi.org/10.1111/all.70094 |
| Publication Year: |
2025 |
| Collection: |
University of Southern Denmark: Research Output / Syddansk Universitet |
| Subject Terms: |
allergen-specific immunotherapy; birch pollen allergy; CD8+ T cells; DNA methylation; epigenome-wide DNA methylation study; HLA; NK cells |
| Description: |
Background: Until now, no study has investigated the impact of allergen immunotherapy (AIT) on genome-wide DNA methylation in a longitudinal set-up. Herein, we investigated whether differences in DNA methylation occur in birch pollen allergic patients undergoing 6 months of birch pollen AIT, assessed alterations in methylation-based blood cell type composition, and correlated DNA methylation to serological AIT biomarkers. Methods: We performed genome-wide DNA-methylation analysis on bisulfite-converted DNA derived from whole blood samples of 16 birch pollen-allergic patients (pre–/post-birch pollen AIT) and 15 placebo (pre-/post-placebo treatment). Results: Our analysis identified cg22187251, located within a regulatory region upstream of the glucosaminyl (N-acetyl) transferase 2 (GCNT2) gene and cg22336863 upstream of the transcription start site of actin binding rho activating protein (ABRA), as hypermethylated. Functional assays revealed that these regions exhibit methylation-dependent promoter and enhancer activities. We identified differentially methylated positions within the HLA gene complex, and an AIT-specific increase of CD8+ T cell populations accompanied by a decrease in natural killer (NK) cell proportion. Strong to moderate correlations with clinical biomarkers (such as specific IgG 4 ) were observed for 42% of the top 100 differentially methylated positions. Conclusion: GCNT2 and ABRA are implicated in Rho-signaling, a pathway involved in Th2 differentiation. GCNT2 modulates the SMAD-dependent TGF-β pathway, indicating a role in mediating AIT-induced immunotolerance. This is the first longitudinal study investigating DNA methylation changes induced by birch pollen AIT. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| ISSN: |
0105-4538; 1398-9995 |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/41065049; info:eu-repo/semantics/altIdentifier/pissn/0105-4538; info:eu-repo/semantics/altIdentifier/eissn/1398-9995 |
| DOI: |
10.1111/all.70094 |
| Availability: |
https://portal.findresearcher.sdu.dk/da/publications/b9aeb02d-b1d6-4ef7-b337-551086d53e04; https://doi.org/10.1111/all.70094; https://findresearcher.sdu.dk/ws/files/299858123/Allergy_-_2025_-_Lahnsteiner_-_Genome_Wide_Blood_DNA_Methylation_Profiling_in_Birch_Pollen_Allergic_Patients_Undergoing.pdf |
| Rights: |
info:eu-repo/semantics/openAccess ; http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.ADC605E2 |
| Database: |
BASE |