Immune fingerprinting of bacterial infections in decompensated cirrhosis

Jacob, Emily 2022. Immune fingerprinting of bacterial infections in decompensated cirrhosis. MPhil Thesis, Cardiff University. Item availability restricted.

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Abstract

Background and Aims Decompensated cirrhosis is associated with an increased risk of infection. Acute-on-chronic liver failure (ACLF) is a severe phenotype associated with immune dysregulation. Immunological phenotypes of individuals with advanced liver disease may enable stratification of patients to specific treatments. The humoral profile in peripheral blood at progressive stages of cirrhosis, contribution to prognosis, and risk of complications is yet to be fully defined. Cellular and humoral profiles in peripheral blood (and ascites where possible) of individuals with cirrhosis were investigated to identifying immunological phenotypes of advanced liver disease. Method Patients were recruited from the hepatology day case and inpatient service at the University Hospital of Wales. Participants were stratified into healthy donors, no acute illness Child-Pugh (CP)-A, no acute illness CP-B, chronic decompensation, acute decompensation (no infection), acute decompensation (infection) and ACLF. Conventional/non-conventional lymphocytes were analysed by multiparameter flow cytometry and 31 analytes were analysed by Luminex multiplex assays comparing analyte concentrations in peripheral blood and ascites. Results ACLF monocytes were significantly elevated compared to no acute illness CP-A, no acute illness CP-B and chronic decompensation no infection. MAIT cells were significantly reduced in no acute illness (CP-B), acute decompensation (no infection) and ACLF patients. Chronic decompensation and ACLF were associated with increased expression of PD1 on ascites CD4+ and CD8+ T cells. Ascites, IL-6, IL-10, VEGF, CXCL10 and CCL2 levels were significantly higher compared to peripheral blood. Conclusion Alterations in the monocytic lineage may correlate with disease severity. Reduction in MAIT cells alongside PD1 overexpression, and subsequent T cell exhaustion, may contribute to immune suppression in advanced liver disease. Future work will apply non-directed clustering as a tool to better stratify patients based on complex immune signatures.

Item Type:	Thesis (MPhil)
Date Type:	Completion
Status:	Unpublished
Schools:	Medicine
Date of First Compliant Deposit:	3 January 2023
Last Modified:	22 Jun 2023 15:47
URI:	https://orca.cardiff.ac.uk/id/eprint/155300

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