Blood and nasal epigenetics correlate with allergic rhinitis symptom development in the environmental exposure unit. Issue 1 (22nd September 2017)

• Record Type: Journal Article
• Authors: North, M. L.; Jones, M. J.; MacIsaac, J. L.; Morin, A. M.; Steacy, L. M.; Gregor, A.; Kobor, M. S.; Ellis, A. K.
• Is Part Of: Allergy. Volume 73:Issue 1(2018)
• Page Start: 196
• Page End: 205
• Publication Date: 2017-09-22
• Subjects: allergen challenge -- allergic rhinitis -- environmental exposure unit -- epigenetics -- pollen; Allergy -- Periodicals; 616.97
• DOI: 10.1111/all.13263
• Languages: English
• ISSNs: 0105-4538

Abstract

Abstract: Background: Epigenetic alterations may represent new therapeutic targets and/or biomarkers of allergic rhinitis (AR). Our aim was to examine genome‐wide epigenetic changes induced by controlled pollen exposure in the environmental exposure unit (EEU). Methods: 38 AR sufferers and eight nonallergic controls were exposed to grass pollen for 3 hours on two consecutive days. We interrogated DNA methylation at baseline and 3 hours in peripheral blood mononuclear cells (PBMCs) using the Infinium Methylation 450K array. We corrected for demographics, cell composition, and multiple testing (Benjamini‐Hochberg) and verified hits using bisulfite PCR pyrosequencing and qPCR. To extend these findings to a clinically relevant tissue, we investigated DNA methylation and gene expression of mucin 4 ( MUC4 ), in nasal brushings from a separate validation cohort exposed to birch pollen. Results: In PBMCs of allergic rhinitis participants, 42 sites showed significant DNA methylation changes of 2% or greater. DNA methylation changes in tryptase gamma 1 ( TPSG1 ), schlafen 12 ( SLFN12 ), and MUC4 in response to exposure were validated by pyrosequencing. SLFN12 DNA methylation significantly correlated with symptoms ( P < 0.05), and baseline DNA methylation pattern was found to be predictive of symptom severity upon grass allergen exposure ( P = 0.029). Changes in MUC4 DNA methylation in nasal brushings in the validation cohort correlated with drop in peak nasal inspiratory flow (Spearman's r = 0.314, P = 0.034), and MUC4 gene expression was significantly increased ( P < 0.0001). Conclusion: This study revealed novel and rapid epigenetic changes upon exposure in a controlled allergen challenge facility, and identified baseline epigenetic status as a predictor of symptom severity.