Soluble Herpes Virus Entry Mediator and Type II/III Interferons Are Upregulated in Primary Biliary Cholangitis

Overview

Journal Int J Mol Sci

Publisher MDPI

Date 2025 Jan 25

PMID 39859319

Authors

Yooyun Chung

Hio Lam Phoebe Tsou

Michael A Heneghan

Shilpa Chokshi

Antonio Riva

Affiliations

Soon will be listed here.

Abstract

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 ( = 0.0404), with increased significance in the ESPBC subgroup ( < 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 ( = 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.

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