Epigenetic Signatures Discriminate Patients With Primary Sclerosing Cholangitis and Ulcerative Colitis From Patients With Ulcerative Colitis
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...
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Frontiers Media S.A.
2022-03-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.840935/full |
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| author | Manon de Krijger Manon de Krijger Ishtu L. Hageman Ishtu L. Hageman Andrew Y. F. Li Yim Jan Verhoeff Jan Verhoeff Juan J. Garcia Vallejo Patricia H. P. van Hamersveld Evgeni Levin Evgeni Levin Theodorus B. M. Hakvoort Manon E. Wildenberg Manon E. Wildenberg Peter Henneman Cyriel Y. Ponsioen Wouter J. de Jonge Wouter J. de Jonge |
| author_facet | Manon de Krijger Manon de Krijger Ishtu L. Hageman Ishtu L. Hageman Andrew Y. F. Li Yim Jan Verhoeff Jan Verhoeff Juan J. Garcia Vallejo Patricia H. P. van Hamersveld Evgeni Levin Evgeni Levin Theodorus B. M. Hakvoort Manon E. Wildenberg Manon E. Wildenberg Peter Henneman Cyriel Y. Ponsioen Wouter J. de Jonge Wouter J. de Jonge |
| author_sort | Manon de Krijger |
| collection | DOAJ |
| 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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| spelling | doaj.art-ecb2a98c38e74c07ac01f6e645bbf90b2022-12-21T23:40:51ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-03-011310.3389/fimmu.2022.840935840935Epigenetic Signatures Discriminate Patients With Primary Sclerosing Cholangitis and Ulcerative Colitis From Patients With Ulcerative ColitisManon de Krijger0Manon de Krijger1Ishtu L. Hageman2Ishtu L. Hageman3Andrew Y. F. Li Yim4Jan Verhoeff5Jan Verhoeff6Juan J. Garcia Vallejo7Patricia H. P. van Hamersveld8Evgeni Levin9Evgeni Levin10Theodorus B. M. Hakvoort11Manon E. Wildenberg12Manon E. Wildenberg13Peter Henneman14Cyriel Y. Ponsioen15Wouter J. de Jonge16Wouter J. de Jonge17Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, NetherlandsDepartment of Gastroenterology and Hepatology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, NetherlandsTytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, NetherlandsDepartment of Gastroenterology and Hepatology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, NetherlandsDepartment of Clinical Genetics, Genome Diagnostics Laboratory, Amsterdam Reproduction and Development, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, NetherlandsTytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, NetherlandsDepartment of Molecular Cell Biology and Immunology, Amsterdam Infection & Immunity and Cancer Center Amsterdam, Amsterdam University Medical Centers, Free University of Amsterdam, Amsterdam, NetherlandsDepartment of Molecular Cell Biology and Immunology, Amsterdam Infection & Immunity and Cancer Center Amsterdam, Amsterdam University Medical Centers, Free University of Amsterdam, Amsterdam, NetherlandsTytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, NetherlandsDepartment of Vascular Medicine, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, NetherlandsHoraizon BV, Delft, NetherlandsTytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, NetherlandsTytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, NetherlandsDepartment of Gastroenterology and Hepatology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, NetherlandsDepartment of Clinical Genetics, Genome Diagnostics Laboratory, Amsterdam Reproduction and Development, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, NetherlandsDepartment of Gastroenterology and Hepatology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, NetherlandsTytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, NetherlandsDepartment of Surgery, University Clinic of Bonn, Bonn, GermanyBackgroundPrimary 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.https://www.frontiersin.org/articles/10.3389/fimmu.2022.840935/fullprimary sclerosing cholangitisulcerative colitisDNA methylation/methylomeperipheral blood850k methylation arraymass cytometry |
| spellingShingle | Manon de Krijger Manon de Krijger Ishtu L. Hageman Ishtu L. Hageman Andrew Y. F. Li Yim Jan Verhoeff Jan Verhoeff Juan J. Garcia Vallejo Patricia H. P. van Hamersveld Evgeni Levin Evgeni Levin Theodorus B. M. Hakvoort Manon E. Wildenberg Manon E. Wildenberg Peter Henneman Cyriel Y. Ponsioen Wouter J. de Jonge Wouter J. de Jonge Epigenetic Signatures Discriminate Patients With Primary Sclerosing Cholangitis and Ulcerative Colitis From Patients With Ulcerative Colitis Frontiers in Immunology primary sclerosing cholangitis ulcerative colitis DNA methylation/methylome peripheral blood 850k methylation array mass cytometry |
| title | Epigenetic Signatures Discriminate Patients With Primary Sclerosing Cholangitis and Ulcerative Colitis From Patients With Ulcerative Colitis |
| title_full | Epigenetic Signatures Discriminate Patients With Primary Sclerosing Cholangitis and Ulcerative Colitis From Patients With Ulcerative Colitis |
| title_fullStr | Epigenetic Signatures Discriminate Patients With Primary Sclerosing Cholangitis and Ulcerative Colitis From Patients With Ulcerative Colitis |
| title_full_unstemmed | Epigenetic Signatures Discriminate Patients With Primary Sclerosing Cholangitis and Ulcerative Colitis From Patients With Ulcerative Colitis |
| title_short | Epigenetic Signatures Discriminate Patients With Primary Sclerosing Cholangitis and Ulcerative Colitis From Patients With Ulcerative Colitis |
| title_sort | epigenetic signatures discriminate patients with primary sclerosing cholangitis and ulcerative colitis from patients with ulcerative colitis |
| topic | primary sclerosing cholangitis ulcerative colitis DNA methylation/methylome peripheral blood 850k methylation array mass cytometry |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.840935/full |
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