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Peripheral Blood DNA Methylation Signatures and Response to Tofacitinib in Moderate-to-severe Ulcerative Colitis.
- Source :
- Journal of Crohn's & Colitis; Aug2024, Vol. 18 Issue 8, p1179-1189, 11p
- Publication Year :
- 2024
-
Abstract
- Introduction Predictive biomarkers for treatment efficacy of ulcerative colitis [UC] treatments are lacking. Here, we performed a longitudinal study investigating the association and potential predictive power of genome-wide peripheral blood [PB] DNA methylation signatures and response to tofacitinib treatment in UC. Methods We recruited moderate-to-severe UC patients starting tofacitinib treatment, and measured PB DNA methylation profiles at baseline [T1], after 8 weeks [T2], and in a subset [ n = 8] after a median of 20 weeks [T3] using the Illumina Infinium HumanMethylation EPIC BeadChip. After 8 weeks, we distinguished responders [R] from non-responders [NR] based on a centrally read endoscopic response [decrease in endoscopic Mayo score ≥1 or Ulcerative Colitis Endoscopic Index of Severity ≥2] combined with corticosteroid-free clinical and/or biochemical response. T1 PB samples were used for biomarker identification, and T2 and publicly available intraclass correlation [ICC] data were used for stability analyses. RNA-sequencing was performed to understand the downstream effects of the predictor CpG loci. Results In total, 16 R and 15 NR patients, with a median disease duration of 7 [4–12] years and overall comparable patient characteristics at baseline, were analysed. We identified a panel of 53 differentially methylated positions [DMPs] associated with response to tofacitinib [AUROC 0.74]. Most DMPs [77%] demonstrated both short- and long-term hyperstability [ICC ≥0.90], irrespective of inflammatory status. Gene expression analysis showed lower FGFR2 [ p <subscript>BH</subscript> = 0.011] and LRPAP1 [ p <subscript>BH</subscript> = 0.020], and higher OR2L13 [p<subscript>BH</subscript> = 0.016] expression at T1 in R compared with NR. Conclusion Our observations demonstrate the utility of genome-wide PB DNA methylation signatures to predict response to tofacitinib. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 18739946
- Volume :
- 18
- Issue :
- 8
- Database :
- Supplemental Index
- Journal :
- Journal of Crohn's & Colitis
- Publication Type :
- Academic Journal
- Accession number :
- 179110668
- Full Text :
- https://doi.org/10.1093/ecco-jcc/jjad129