TY - JOUR
T1 - Epigenetic Signatures Discriminate Patients With Primary Sclerosing Cholangitis and Ulcerative Colitis From Patients With Ulcerative Colitis
AU - de Krijger, Manon
AU - Hageman, Ishtu L.
AU - Li Yim, Andrew Y. F.
AU - Verhoeff, Jan
AU - Garcia Vallejo, Juan J.
AU - van Hamersveld, Patricia H. P.
AU - Levin, Evgeni
AU - Hakvoort, Theodorus B. M.
AU - Wildenberg, Manon E.
AU - Henneman, Peter
AU - Ponsioen, Cyriel Y.
AU - de Jonge, Wouter J.
N1 - Funding Information:
ALY was funded by the European Union’s Horizon 2020 research and innovation program under Grant Agreement No. ITN-2014-EID-641665. ALY and IH were funded by the Helmsley charitable trust.
Publisher Copyright:
Copyright © 2022 de Krijger, Hageman, Li Yim, Verhoeff, Garcia Vallejo, van Hamersveld, Levin, Hakvoort, Wildenberg, Henneman, Ponsioen and de Jonge.
PY - 2022/3/16
Y1 - 2022/3/16
N2 - Background: Primary 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. Methods: The 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. Results: Genome 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. Conclusion: DNA methylation enables discerning PSC-UC from UC patients, with a potential for biomarker development.
AB - Background: Primary 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. Methods: The 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. Results: Genome 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. Conclusion: DNA methylation enables discerning PSC-UC from UC patients, with a potential for biomarker development.
KW - 850k methylation array
KW - DNA methylation/methylome
KW - mass cytometry
KW - peripheral blood
KW - primary sclerosing cholangitis
KW - ulcerative colitis
UR - http://www.scopus.com/inward/record.url?scp=85127528086&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2022.840935
DO - 10.3389/fimmu.2022.840935
M3 - Article
C2 - 35371111
SN - 1664-3224
VL - 13
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 840935
ER -