Kati, Danai;
(2024)
Biomarker discovery for UDCA response evaluation in Primary Biliary Cholangitis.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Primary biliary cholangitis (PBC) is an autoimmune disease of the small intralobular bile ducts, affecting 1 in 1000 people worldwide, mostly women. First line therapy is ursodeoxycholic acid (UDCA). All patients are treated with UDCA for a year, but only 60% respond to this therapy. After one year of unsuccessful treatment the disease typically progresses to a later stage for which there is no effective therapy. There are no established clinical tests or biomarkers to identify non-responding patients prior to initiation of treatment. Using mass spectrometry-based proteomics, I analysed the serum of female UK PBC patients who had undergone UDCA therapy. The patients were separated into responders (n=40) and non-responders (n=40), and a matched control group of healthy women (n=40). Age (around 60), fibrosis stage and other biochemical and medical conditions were factored into the selection of all subjects. Based on changes in circulating proteins, my results indicate that there is a specific proteomic fingerprint in non-responder patients’ sera. Multiple altered proteins in this fingerprint are involved in the immune response and in lipid metabolism. A subset of the altered proteins are known to be associated with the disease and with a UDCA response. Soluble intercellular adhesion molecule-1 (sICAM-1), apolipoprotein E (APOE) and polymeric immunoglobulin receptor (PIGR) were verified in single serum and plasma samples from the UK and US populations. sICAM-1 and PIGR are promising biomarker candidates for prediction and evaluation of UDCA response. Their clinical importance comes from their potential to distinguish responders from non-responders and thereby allow the latter to undergo an alternative treatment (fenofibrates) without wasting a year on an unproductive treatment.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Biomarker discovery for UDCA response evaluation in Primary Biliary Cholangitis |
| Language: | English |
| Additional information: | Copyright © The Author 2024. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10199875 |
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