Regulation of immune responses in primary biliary cholangitis: a transcriptomic analysis of peripheral immune cells

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Mulcahy, Victoria, Liaskou, Evaggelia, Martin, Jose Ezequiel, Kotagiri, Prasanti, Badrock, Jonathan, Jones, Rebecca L., Rushbrook, Simon M., Ryder, Stephen D., Thorburn, Douglas, Taylor-Robinson, Simon D., Clark, Graeme, Cordell, Heather J., Sandford, Richard N., Jones, David E., Hirschfield, Gideon M. and Mells, George F. (2023) Regulation of immune responses in primary biliary cholangitis: a transcriptomic analysis of peripheral immune cells. Hepatology Communications, 7 (4). pp. 1-14. ISSN 2471-254X

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Abstract

Background & Aims: In patients with primary biliary cholangitis (PBC), the serum liver biochemistry measured during treatment with ursodeoxycholic acid-the UDCA response-accurately predicts long-term outcome. Molecular characterization of patients stratified by UDCA response can improve biological understanding of the high-risk disease, thereby helping to identify alternative approaches to disease-modifying therapy. In this study, we sought to characterize the immunobiology of the UDCA response using transcriptional profiling of peripheral blood mononuclear cell subsets.  Methods: We performed bulk RNA-sequencing of monocytes and TH1, TH17, TREG, and B cells isolated from the peripheral blood of 15 PBC patients with adequate UDCA response (“responders”), 16 PBC patients with inadequate UDCA response (“nonresponders”), and 15 matched controls. We used the Weighted Gene Co-expression Network Analysis to identify networks of co-expressed genes (“modules”) associated with response status and the most highly connected genes (“hub genes”) within them. Finally, we performed a Multi-Omics Factor Analysis of the Weighted Gene Co-expression Network Analysis modules to identify the principal axes of biological variation (“latent factors”) across all peripheral blood mononuclear cell subsets.  Results: Using the Weighted Gene Co-expression Network Analysis, we identified modules associated with response and/or disease status (q < 0.05) in each peripheral blood mononuclear cell subset. Hub genes and functional annotations suggested that monocytes are proinflammatory in nonresponders, but antiinflammatory in responders; TH1 and TH17 cells are activated in all PBC cases but better regulated in responders; and TREG cells are activated-but also kept in check-in responders. Using the Multi-Omics Factor Analysis, we found that antiinflammatory activity in monocytes, regulation of TH1 cells, and activation of TREG cells are interrelated and more prominent in responders. Conclusions: We provide evidence that adaptive immune responses are better regulated in patients with PBC with adequate UDCA response.

Item Type: Article
Additional Information: ACKNOWLEDGMENTS The authors thank the staff at the National Institute for Health Research (NIHR) Cambridge BioResource for their assistance in recruiting healthy volunteers. Simon D. Taylor-Robinson thanks the British National Institute for Health Research Biomedical Facility at Imperial College London for infrastructure support. Evaggelia Liaskou thanks the Flow Cytometry Platform at the University of Birmingham for support with cell sorting experiments. Finally, they thank all participants in the study for giving up their time and for providing samples. This paper presents independent research supported by the NIHR Birmingham Biomedical Research Centre at the University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care.
Uncontrolled Keywords: hepatology ,/dk/atira/pure/subjectarea/asjc/2700/2721
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology
Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
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Depositing User: LivePure Connector
Date Deposited: 16 Jul 2026 13:41
Last Modified: 16 Jul 2026 13:41
URI: https://ueaeprints.uea.ac.uk/id/eprint/103902
DOI: 10.1097/HC9.0000000000000110

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