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Local microRNAs in peritoneal dialysis-related peritonitis

Brook, Amy 2019. Local microRNAs in peritoneal dialysis-related peritonitis. PhD Thesis, Cardiff University.
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Abstract

Infection remains a major cause of morbidity, mortality and technique failure in PD patients. Identification of peritonitis episodes and the causative organism is slow and unreliable. The immune system has evolved to be specific for different pathogens, suggesting a pathogen specific “immune fingerprint” may be able to distinguish distinct pathogens to guide more accurate treatment decisions. microRNAs are post-transcriptional regulators of most human genes and have roles in the majority of biological processes and pathways. They are stable, accurate and specific biomarkers in biological fluids. My work aimed to combine the immune fingerprint model with specific microRNAs in PD effluent to identify peritonitis episodes and ascertain the role of extracellular microRNAs in the acute immune response. Approach The microRNA profile of PD effluent was analysed in peritonitis patients with different infectious organisms to identify candidate biomarkers. The cellular source of these microRNAs was identified, and the functional release of one microRNA (miR-223) into the extracellular space was analysed for functional stabilisation in extracellular vesicles. Results microRNA profiles are altered in infected compared to uninfected PD effluent, which may have diagnostic value in acute peritonitis. Four microRNAs were identified as candidate biomarkers (miR-223, miR-27a, miR-21 and miR-31), with distinct cell-specific expression patterns. Potential mRNA targets of these microRNAs were identified. miR-223 was found to be functionally stabilised in PD effluent from peritonitis patients, with a proportion likely to be incorporated into neutrophil-derived exosomes. Conclusions My studies prove that microRNAs are useful biomarkers of infection in PD-related peritonitis and have the potential to contribute to a pathogen-specific immune fingerprint. Exosome-encapsulated microRNAs may have a functional role in intercellular signalling between immune cells responding to the infection and the local tissue, to help clear the infection and resolve the inflammation.

Item Type: Thesis (PhD)
Date Type: Completion
Status: Unpublished
Schools: Medicine
Date of First Compliant Deposit: 3 May 2019
Last Modified: 03 May 2019 09:45
URI: http://orca-mwe.cf.ac.uk/id/eprint/122115

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