{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T11:58:37Z","timestamp":1778932717756,"version":"3.51.4"},"reference-count":52,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T00:00:00Z","timestamp":1759968000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004543","name":"China Scholarship Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Until now, no study has investigated the impact of allergen immunotherapy (AIT) on genome\u2010wide DNA methylation in a longitudinal set\u2010up. Herein, we investigated whether differences in DNA methylation occur in birch pollen allergic patients undergoing 6\u2009months of birch pollen AIT, assessed alterations in methylation\u2010based blood cell type composition, and correlated DNA methylation to serological AIT biomarkers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed genome\u2010wide DNA\u2010methylation analysis on bisulfite\u2010converted DNA derived from whole blood samples of 16 birch pollen\u2010allergic patients (pre\u2013\/post\u2010birch pollen AIT) and 15 placebo (pre\u2010\/post\u2010placebo treatment).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Our analysis identified cg22187251, located within a regulatory region upstream of the glucosaminyl (N\u2010acetyl) transferase 2 (\n                      <jats:italic>GCNT2<\/jats:italic>\n                      ) gene and cg22336863 upstream of the transcription start site of actin binding rho activating protein (\n                      <jats:italic>ABRA<\/jats:italic>\n                      ), as hypermethylated. Functional assays revealed that these regions exhibit methylation\u2010dependent promoter and enhancer activities. We identified differentially methylated positions within the HLA gene complex, and an AIT\u2010specific 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\n                      <jats:sub>4<\/jats:sub>\n                      ) were observed for 42% of the top 100 differentially methylated positions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      <jats:italic>GCNT2<\/jats:italic>\n                      and\n                      <jats:italic>ABRA<\/jats:italic>\n                      are implicated in Rho\u2010signaling, a pathway involved in Th2 differentiation. GCNT2 modulates the SMAD\u2010dependent TGF\u2010\u03b2 pathway, indicating a role in mediating AIT\u2010induced immunotolerance. This is the first longitudinal study investigating DNA methylation changes induced by birch pollen AIT.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/all.70094","type":"journal-article","created":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T10:23:13Z","timestamp":1760005393000},"page":"3412-3423","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Genome\u2010Wide Blood\n                    <scp>DNA<\/scp>\n                    Methylation Profiling in Birch Pollen Allergic Patients Undergoing Allergen\u2010Specific Immunotherapy"],"prefix":"10.1111","volume":"80","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7402-3369","authenticated-orcid":false,"given":"Angelika","family":"Lahnsteiner","sequence":"first","affiliation":[{"name":"Department of Biosciences and Medical Biology Paris Lodron University of Salzburg  Salzburg Austria"},{"name":"Center for Tumor Biology and 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