Related Experiment Video
Updated: Jun 14, 2025
Screening Assays to Characterize Novel Endothelial Regulators Involved in the Inflammatory Response
Published on: September 15, 2017
Learning from serum markers reflecting endothelial activation: longitudinal data in childhood-onset systemic lupus
Sandy C Bergkamp1, Nick D Bergkamp2, Mohamed Javad Wahadat3,4
1Department of Paediatric Immunology, Rheumatology and Infectious Diseases, Emma Children's Hospital, Amsterdam University Medical Centres (AUMC), University of Amsterdam, Amsterdam, The Netherlands s.c.bergkamp@amsterdamumc.nl.
Insights
Childhood-onset SLE (cSLE) is linked to endothelial dysfunction, increasing atherosclerosis risk. While treatment normalized many markers, some remained elevated, suggesting a persistent role for endothelial dysregulation in cSLE.
Area of Science:
- Pediatric Rheumatology
- Cardiovascular Research
- Immunology
Background:
- Childhood-onset Systemic Lupus Erythematosus (cSLE) patients face heightened risks of premature atherosclerosis.
- Endothelial dysfunction is a key factor in cSLE-related cardiovascular complications.
- Understanding the mechanisms of endothelial involvement in cSLE is crucial for risk mitigation.
Purpose of the Study:
- To longitudinally measure endothelial cell (EC) function markers and lipids in cSLE patients compared to healthy controls (HC).
- To assess the correlation of these markers with disease activity (SLEDAI) and nailfold capillaroscopy findings.
- To investigate the long-term impact of endothelial dysregulation in cSLE.
Main Methods:
- Longitudinal analysis of serum samples from a multicenter cSLE cohort and age/sex-matched HC.
- Measurement of 15 EC markers and 6 lipids at two time points.
- Evaluation of disease activity using SLEDAI and nailfold videocapillaroscopy scoring.
Main Results:
- Elevated levels of angiopoietin-2, CCL2, CXCL10, GAS6, pentraxin-3, thrombomodulin, VCAM-1, and vWF-A2 were observed in cSLE patients at baseline.
- Many elevated EC markers normalized post-treatment.
- Angiopoietin-2, CCL2, CXCL10, GAS6, thrombomodulin, and VCAM-1 remained significantly elevated in a subset of cSLE patients even with low disease activity.
Conclusions:
- Endothelial activation markers are dysregulated in cSLE patients.
- Persistent elevation of certain EC markers suggests a role for endothelial dysfunction beyond active disease phases.
- Targeting endothelial pathways may be beneficial for managing cardiovascular risks in cSLE.
Objectives:
In childhood-onset SLE (cSLE), patients have an increased risk of premature atherosclerosis. The pathophysiological mechanisms for this premature atherosclerosis are not yet completely understood, but besides traditional risk factors, the endothelium plays a major role. The first aim of this study was to measure levels of SLE-associated markers involved in endothelial cell (EC) function and lipids in a cSLE cohort longitudinally in comparison with healthy controls (HC). Next aim was to correlate these levels with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and nailfold capillaroscopic patterns.
Methods:
Blood serum samples, videocapillaroscopy images and patient characteristics were collected in a multicentre longitudinal cSLE cohort and from age and sex comparable HC. Disease activity was evaluated by SLEDAI. A total of 15 EC markers and six lipids were measured in two longitudinal cSLE samples (minimum interval of 6 months) and in HC. Nailfold videocapillaroscopy images were scored according to the guidelines from the EULAR Study Group on Microcirculation in Rheumatic Diseases.
Results:
In total, 47 patients with cSLE and 42 HCs were analysed. Median age at diagnosis was 15 years (IQR 12-16 years). Median time between t=1 and t=2 was 14.5 months (IQR 9-24 months). Median SLEDAI was 12 (IQR 6-18) at t=1 and 2 (IQR 1-4) at t=2. Serum levels of angiopoietin-2, CCL2, CXCL10, GAS6, pentraxin-3, thrombomodulin, VCAM-1 and vWF-A2 were elevated in cSLE compared with HC at t=1. While many elevated EC markers at t=1 normalised over time after treatment, several markers remained significantly increased compared with HC (angiopoietin-2, CCL2, CXCL10, GAS6, thrombomodulin and VCAM-1).
Conclusion:
In serum from patients with cSLE different markers of endothelial activation were dysregulated. While most markers normalised during treatment, others remained elevated in a subset of patients, even during low disease activity. These results suggest a role for the dysregulated endothelium in early and later phases of cSLE, possibly also during lower disease activity.
Trial Registration Number:
NL60885.018.17.
More Related Videos
09:43Analyses of Proteinuria, Renal Infiltration of Leukocytes, and Renal Deposition of Proteins in Lupus-prone MRL/lpr Mice
Published on: June 8, 2022
07:45Harvest of Endothelial Cells from the Balloon Tips of Swan-Ganz Catheters after Right Heart Catheterization
Published on: January 23, 2019
