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Immune Activation in Primary Sclerosing Cholangitis: A Systematic Review and Comparative Analysis With Inflammatory
Md Moniruzzaman1,2,3, Ayesha Shah3, Thomas Fairlie1,3
1Faculty of Health, Medicine, and Behavioural Sciences, The University of Queensland, Translational Research Institute, Brisbane, Australia.
Background And Objectives:
Primary sclerosing cholangitis (PSC) is a chronic liver disease with aberrant immune dysregulation and bile duct fibrosis. It is often associated with inflammatory bowel disease (IBD), especially ulcerative colitis, raising questions about distinct immune activation in these conditions. Therefore, we aimed to systematically review and compare immune activation patterns in patients with PSC and IBD (without PSC), which may provide deeper insights into PSC pathophysiology.
Methods:
MEDLINE, Scopus, Cochrane Library, and Embase were searched until July 2024 for relevant studies reporting immune cell profiles, cytokine levels, and gene expression patterns in patients with PSC. Reference articles of patients with IBD were then added to compare the immune profile of patients with PSC (with or without IBD) and patients with IBD-only.
Results:
Twenty-three articles studying 638 PSC and 557 non-PSC non-IBD subjects were included. PSC patients showed various degrees of immune activation in the systemic circulation, biliary fluid, and liver tissue, most notably regarding integrin β7+ gut-homing T cells, IL-2, and IL-10 compared to their respective controls. Compared with patients with IBD, patients with PSC had reduced Tregs in the systemic circulation. When comparing tissue-based immune markers, PSC-livers had increased Th17 cells, IL-1β, and TNF-α and reduced levels of B cells, IL-2, and IL-10 than the IBD-mucosa.
Conclusions:
Patients with PSC and patients with IBD without PSC can be differentiated by a distinct immune activation pattern with upregulation of Th17 and downregulation of Treg functions in PSC while other immune parameters do not allow a differentiation of these conditions.
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