Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Circulating blood immunophenotyping and metabolite profiling in pulmonary vascular diseases

Zalewska, Kasia 2018. Circulating blood immunophenotyping and metabolite profiling in pulmonary vascular diseases. MD Thesis, Cardiff University.
Item availability restricted.

[thumbnail of 2018ZalewskaK  MD  DEC pages removed.pdf] PDF - Accepted Post-Print Version
Download (6MB)
[thumbnail of 2018ZalewskaK Thesis Publication-form.pdf] PDF - Supplemental Material
Restricted to Repository staff only

Download (658kB)


Pulmonary hypertension is an abnormal physiological state associated with a variety of medical conditions. However, the ability to accurately phenotype disease subtypes within this heterogeneous syndrome is limited. In this thesis, I utilised advanced phenotyping techniques, guided by pathophysiological processes known to be dysregulated in pulmonary vascular diseases; immunity and metabolism. I used flow cytometry based immunophenotyping to study circulating leukocyte subpopulations and metabolomic analysis to study metabolite profiles in circulating blood. I hypothesised that there would be differences between disease and health, and differences between disease subgroups. In the immunophenotyping studies, I identified an immune cell signature in Idiopathic Pulmonary Arterial Hypertension (IPAH) and Heritable Pulmonary Arterial Hypertension (HPAH) characterised by increased frequencies of T follicular helper (Tfh) cells, plasmablasts and PD1-expressing CD8+ T cells. This signature was not found in Chronic Thromboembolic Pulmonary Hypertension (CTEPH). These findings support the hypothesis that dysfunctional immune activation may be implicated in IPAH pathobiology, and that IPAH and HPAH may have shared immunopathological mechanisms. In the metabolomic studies, I identified wide ranging metabolic changes in pulmonary vascular disease, including evidence of disrupted energy metabolism, increased cellular proliferation and reduction in antioxidant metabolites. Additionally, by comparing paired samples from different anatomical sites, it was possible to differentiate metabolic perturbations which are localised to specific anatomical sub-compartments. Key to the clinical applications of this research, I have demonstrated immunological and metabolic alterations which are a shared feature amongst different pulmonary vascular disease subgroups, but also some changes which are specific to disease subsets. Future advances in disease phenotyping may facilitate effective new targeted therapy for pulmonary vascular diseases.

Item Type: Thesis (MD)
Date Type: Completion
Status: Unpublished
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
Date of First Compliant Deposit: 29 May 2018
Last Modified: 07 Sep 2021 11:14

Actions (repository staff only)

Edit Item Edit Item


Downloads per month over past year

View more statistics