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The vasculopathy of Juvenile Dermatomyositis

Papadopoulou, Charalampia; (2019) The vasculopathy of Juvenile Dermatomyositis. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

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.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: The vasculopathy of Juvenile Dermatomyositis
Event: UCL
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Copyright © The Author 2019. Original content in this thesis is licensed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/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
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 Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10078490
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