{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T22:40:00Z","timestamp":1782859200145,"version":"3.54.5"},"reference-count":68,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T00:00:00Z","timestamp":1736726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Association for the Study of the Liver Registry Grant (Liver Disease in Pregnancy)"},{"name":"The King\u2019s College Hospital NHS Trust Charity (Orpin Bequest)"},{"name":"The Kelly Group"},{"name":"Foundation for Liver Research and King\u2019s College Hospital (London, UK)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Bacterial translocation-induced inflammation and immune dysfunction are recognised factors contributing to the pathogenesis of primary biliary cholangitis (PBC). However, the specific involvement of interferons (IFNs) and soluble checkpoints (sol-CRs) in shaping the immune landscape in PBC patients remains unexplored. Furthermore, the influence of ursodeoxycholic acid (UDC) on these immune mediators is unknown. Twenty-eight cytokines and 14 sol-CRs were quantified by Luminex assays in plasma samples from 64 PBC patients and 10 healthy controls (HCs). D-lactate was measured as a marker of bacterial translocation. The PBC subgroups were: 24 UDC responders (UDCRs), 18 UDC non-responders (UDCNRs) and 22 patients with end-stage cirrhotic PBC (ESPBC). Soluble herpes virus entry mediator (HVEM) was upregulated in the UDCR subgroup compared to the HC group (p = 0.0404), with increased significance in the ESPBC subgroup (p &lt; 0.0001). There was a progressive increase in several sol-CRs, particularly soluble CD80, LAG3 and CD137 in ESPBC patients. IFN-gamma was higher in the ESPBC subgroup compared to the UDCR subgroup. Elevated IFN-gamma in the UDCNR subgroup compared to UDCR was more significant on excluding patients with cirrhosis (p = 0.0056). Patients with ESPBC expressed several pro-inflammatory cytokines including IL-6, TNF-alpha and CXCL10 compared to the HC group. IFN-lambda-3, but not IFN-lambda-2, was elevated in the ESPBC subgroup compared to all other subgroups. D-lactate levels were equally elevated in all PBC subgroups compared to the HC group. This study provides valuable insights into the immune landscape of PBC, highlighting potential biomarkers and cytokine signatures associated with disease severity and treatment response. Further investigation into the mechanistic roles may pave the way for more targeted therapeutic interventions in PBC management.<\/jats:p>","DOI":"10.3390\/ijms26020605","type":"journal-article","created":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T07:40:08Z","timestamp":1736754008000},"page":"605","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Soluble Herpes Virus Entry Mediator and Type II\/III Interferons Are Upregulated in Primary Biliary Cholangitis"],"prefix":"10.3390","volume":"26","author":[{"given":"Yooyun","family":"Chung","sequence":"first","affiliation":[{"name":"The Roger Williams Institute of Liver Studies, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King\u2019s College London & Foundation for Liver Research, London SE5 9NT, UK"},{"name":"King\u2019s College Hospital, London SE5 9RS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7705-7820","authenticated-orcid":false,"given":"Hio Lam Phoebe","family":"Tsou","sequence":"additional","affiliation":[{"name":"The Roger Williams Institute of Liver Studies, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King\u2019s College London & Foundation for Liver Research, London SE5 9NT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Heneghan","sequence":"additional","affiliation":[{"name":"The Roger Williams Institute of Liver Studies, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King\u2019s College London & Foundation for Liver Research, London SE5 9NT, UK"},{"name":"King\u2019s College Hospital, London SE5 9RS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shilpa","family":"Chokshi","sequence":"additional","affiliation":[{"name":"The Roger Williams Institute of Liver Studies, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King\u2019s College London & Foundation for Liver Research, London SE5 9NT, UK"},{"name":"Peninsula Medical School, Faculty of Health, University of Plymouth, Plymouth PL4 8AA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4974-2780","authenticated-orcid":false,"given":"Antonio","family":"Riva","sequence":"additional","affiliation":[{"name":"The Roger Williams Institute of Liver Studies, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King\u2019s College London & Foundation for Liver Research, London SE5 9NT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"(2017). 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