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

Autor: 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, Mells, George F
Přispěvatelé: Mulcahy, Victoria [0000-0001-7091-4789], Liaskou, Evaggelia [0000-0002-9820-4698], Martin, Jose-Ezequiel [0000-0002-0051-8868], Kotagiri, Prasanti [0000-0002-9806-4349], Ryder, Stephen D [0000-0001-9649-4444], Thorburn, Douglas [0000-0002-5610-5448], Taylor-Robinson, Simon D [0000-0002-8811-1834], Clark, Graeme [0000-0002-5543-2789], Cordell, Heather J [0000-0002-1879-5572], Jones, David E [0000-0002-0083-5564], Hirschfield, Gideon M [0000-0002-6736-2255], Mells, George F [0000-0002-7962-5286], Apollo - University of Cambridge Repository
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Popis: 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
Databáze: OpenAIRE