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Title: The vasculopathy of Juvenile Dermatomyositis
Author: Papadopoulou, Charalampia
ISNI:       0000 0004 7970 7024
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2019
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Vasculopathy is considered central to the pathogenesis of Juvenile Dermatomyositis (JDM). One major hurdle to the study and detection of vasculopathy of JDM and to the monitoring of its progression over time has been the lack of non-invasive biomarkers. Therefore, defining disease activity trajectories relating to persistent endothelial injury in JDM currently remains challenging. This thesis addressed this unmet need by examining biomarkers of endothelial injury, subclinical inflammation and hypercoagulability in a large cohort of JDM patients. Circulating endothelial cells (CEC) were higher in patients with active JDM compared to patients with inactive disease and healthy controls. Total circulating microparticles (MP) counts were also significantly higher in JDM patients compared to healthy controls. These circulating MP were predominantly of platelet and endothelial origin. Enhanced plasma thrombin generation was demonstrated in active compared to inactive JDM and controls. When the inflammatory protein profile associated with endothelial activation and dysfunction in children with JDM was investigated, a number of cytokines/chemokines and adhesion molecules were shown to be elevated in patients with JDM. Levels of galectin-9 strongly correlated with other markers of disease activity. Lastly, increased arterial stiffness was also detected in children with JDM, suggestive of an increased risk of cardiovascular disease and premature atherosclerosis. In conclusion, this thesis demonstrated: 1. Increased endothelial injury in children with active JDM associated with high levels of CEC and circulating MP with propensity to drive thrombin generation and hence occlusive vasculopathy; and 2. Increased arterial stiffness in paediatric patients with JDM. These novel non-invasive biomarkers relating to the vasculopathy of JDM can now be used to track endothelial injury relating to subclinical disease activity in JDM over time and may facilitate development of stratified treatment approaches to reduce long-term adverse outcomes for these children.
Supervisor: Eleftheriou, D. ; Brogan, P. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available