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Title: Studies of serology and vascular ultrasound in patients with systemic lupus erythematosus : focus on cardiovascular disease
Author: Jesus Cameira Croca, S.
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2016
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Abstract:
Systemic lupus erythematosus (SLE) is a multisystem, autoimmune disease characterised by the presence of autoantibodies. Active inflammation in patients with SLE can cause clinical effects in various organs and serum biomarkers can be helpful in monitoring the disease. Over time, patients with SLE have an increased risk of developing atherosclerosis. This risk is partially due to standard risk factors such as smoking and hypertension, but also due to SLE-specific immunological factors. In this thesis I have studied three linked questions; 1) Systemic inflammation can lead to endothelial activation and increased release of nitric oxide. This leads to nitration of serum proteins. Using capture ELISA, I studied levels of nitrated nuclesosomes and nitrated albumin in patients with SLE. Nitrated nucleosome levels were higher in patients with SLE than controls, and were related to some forms of disease activity notably in the central nervous system, but not atherosclerosis. 2) High-density lipoprotein (HDL) and its main structural component, apolipoprotein A1 (ApoA1), have an atheroprotective role. Using direct ELISA, I measured serum levels of anti-ApoA1 and anti-HDL antibodies in patients with SLE. IgG anti-apoA1 levels were associated with increased disease activity and with drug treatment, but not with atherosclerosis. 3) Previous authors used vascular ultrasound to demonstrate asymptomatic carotid plaque in between 30% and 40% of patients with SLE. I used new, more sensitive measures of carotid and femoral atherosclerosis in 100 patients with no previous history of CVD to investigate the factors associated with presence, area, volume and echogenicity of plaque. Thirty-six patients had plaque. Intima-media thickness (IMT) was associated with age and disease duration but not activity. Total plaque area (TPA), however, was increased in patients with persistently active disease and also with anti-HDL levels. Lipid profile was associated with both IMT and TPA. Plaque echogenicity was associated with disease activity and renal function. Comparison of these 100 SLE patients with an age/sex matched control group showed significant differences in morphology and echogenicity of plaque.
Supervisor: Rahman, A. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.790090  DOI: Not available
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