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Academic Journal
Epigenetic Signatures Discriminate Patients With Primary Sclerosing Cholangitis and Ulcerative Colitis From Patients With Ulcerative Colitis
Manon de Krijger, Ishtu L. Hageman, Andrew Y. F. Li Yim, Jan Verhoeff, Juan J. Garcia Vallejo, Patricia H. P. van Hamersveld, Evgeni Levin, Theodorus B. M. Hakvoort, Manon E. Wildenberg, Peter Henneman, Cyriel Y. Ponsioen, Wouter J. de Jonge
Frontiers in Immunology, Vol 13 (2022)
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| Title | Epigenetic Signatures Discriminate Patients With Primary Sclerosing Cholangitis and Ulcerative Colitis From Patients With Ulcerative Colitis |
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| Authors | Manon de Krijger, Ishtu L. Hageman, Andrew Y. F. Li Yim, Jan Verhoeff, Juan J. Garcia Vallejo, Patricia H. P. van Hamersveld, Evgeni Levin, Theodorus B. M. Hakvoort, Manon E. Wildenberg, Peter Henneman, Cyriel Y. Ponsioen, Wouter J. de Jonge |
| Publication Year |
2022
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| Source |
Frontiers in Immunology, Vol 13 (2022)
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| Description |
BackgroundPrimary sclerosing cholangitis (PSC) is a chronic inflammatory liver disease affecting the intra- and extrahepatic bile ducts, and is strongly associated with ulcerative colitis (UC). In this study, we explored the peripheral blood DNA methylome and its immune cell composition in patients with PSC-UC, UC, and healthy controls (HC) with the aim to develop a predictive assay in distinguishing patients with PSC-UC from those with UC alone.MethodsThe peripheral blood DNA methylome of male patients with PSC and concomitant UC, UC and HCs was profiled using the Illumina HumanMethylation Infinium EPIC BeadChip (850K) array. Differentially methylated CpG position (DMP) and region (DMR) analyses were performed alongside gradient boosting classification analyses to discern PSC-UC from UC patients. As observed differences in the DNA methylome could be the result of differences in cellular populations, we additionally employed mass cytometry (CyTOF) to characterize the immune cell compositions.ResultsGenome wide methylation analysis did not reveal large differences between PSC-UC and UC patients nor HCs. Nonetheless, using gradient boosting we were capable of discerning PSC-UC from UC with an area under the receiver operator curve (AUROC) of 0.80. Four CpG sites annotated to the NINJ2 gene were found to strongly contribute to the predictive performance. While CyTOF analyses corroborated the largely similar blood cell composition among patients with PSC-UC, UC and HC, a higher abundance of myeloid cells was observed in UC compared to PSC-UC patients.ConclusionDNA methylation enables discerning PSC-UC from UC patients, with a potential for biomarker development.
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| Document Type |
article
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| Language |
English
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| Publisher Information |
Frontiers Media S.A., 2022.
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| Subject Terms | |
