Metabolic profiling of Autoimmune-related diseases using Molecular Phenomics

Primary Biliary Cholangitis (PBC, formerly known as Primary Biliary Cirrhosis) is a chronic autoimmune cholestatic liver disease, characterised by progressive bile duct damage as a result of decreased bile flow due to impaired secretion by hepatocytes or through bile flow obstruction [1]. The unique pathogenesis of PBC, is defined as a prototypical autoimmune disease, with the presentation of anti-mitochondrial antibodies, resulting in inflammation localized to small intrahepatic bile ductules leading to a spectrum of cholangitis and biliary cirrhosis. Little is known about the aetiology of the disease or the mechanism of treatment, and prognosis remains poor. The UK-PBC Nested Cohort study is a Medical Research Council funded project (REC ref 14/NW/1146), focusing on a multi-omic approach for global profiling approach with metabonomic, transcriptomic, genomic and proteomic data acquired from >600 patients. To date, full NMR and UPLC-MS data acquisition has been conducted. The Urine 1H NMR analysis results from the study are explained in detail and explore some issues with data acquisition. Preliminary results from serum and faecal samples are also explored. This work will then be correlated with the MS data, and used for integration with genomic data, in the hopes of uncovering a better understanding of the disease and its treatment.

The aim of this project is to investigate and identify potential metabolites that may contribute to and are associated PBC, to create a global metabolite expression profile and for potential disease biomarkers.