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Updated: Dec 11, 2025
On-Chip Endothelial Inflammatory Phenotyping
Published on: July 21, 2012
Biomarker profiles of endothelial activation and dysfunction in rare systemic autoimmune diseases: implications for
Judith Wienke1, Jorre S Mertens1,2,3, Samuel Garcia1,2
1Centre for Translational Immunology, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands.
Insights
Chronic inflammatory connective tissue diseases (CICTD) show distinct vascular biomarker profiles linked to disease activity. Some patients exhibit persistent inflammation markers, suggesting ongoing subclinical issues and increased cardiovascular risk.
Area of Science:
- Rheumatology and Immunology
- Vascular Biology
- Biomarker Discovery
Background:
- Vasculopathy is a key feature of chronic inflammatory connective tissue diseases (CICTD), increasing cardiovascular risk.
- Understanding disease-specific biomarkers for endothelial dysfunction and inflammation is crucial in rare CICTD.
Purpose of the Study:
- To investigate disease-specific serum protein profiles in rare CICTD.
- To correlate these profiles with endothelial dysfunction, angiogenic homeostasis, and inflammation.
- To examine the relationship between biomarker profiles and disease activity.
Main Methods:
- Multiplex immunoassay of 38 serum proteins in patients with localized scleroderma, eosinophilic fasciitis, and dermatomyositis, plus controls.
- Analysis included unsupervised clustering, correlation, t-tests, and ANOVA.
- Samples included treatment-naive patients and follow-up during treatment.
Main Results:
- Distinct biomarker profiles were identified for systemic CICTD, eosinophilic fasciitis (EF), and dermatomyositis, with specific signature markers.
- Dermatomyositis and EF shared upregulated markers related to interferon, endothelial activation, and angiogenesis inhibition.
- Profiles correlated with disease activity and mostly normalized with treatment, but a subgroup showed persistent elevations indicating potential subclinical inflammation.
Conclusions:
- CICTD biomarker profiles indicate an anti-angiogenic, interferon-driven state during active disease.
- Incomplete normalization of biomarkers suggests ongoing vascular issues under treatment.
- Further monitoring of vascular biomarkers and targeted interventions are needed to mitigate long-term cardiovascular risk.
Objectives:
Vasculopathy is an important hallmark of systemic chronic inflammatory connective tissue diseases (CICTD) and is associated with increased cardiovascular risk. We investigated disease-specific biomarker profiles associated with endothelial dysfunction, angiogenic homeostasis and (tissue) inflammation, and their relation to disease activity in rare CICTD.
Methods:
A total of 38 serum proteins associated with endothelial (dys)function and inflammation were measured by multiplex-immunoassay in treatment-naive patients with localized scleroderma (LoS, 30), eosinophilic fasciitis (EF, 8) or (juvenile) dermatomyositis (34), 119 (follow-up) samples during treatment, and 65 controls. Data were analysed by unsupervised clustering, Spearman correlations, non-parametric t test and ANOVA.
Results:
The systemic CICTD, EF and dermatomyositis, had distinct biomarker profiles, with 'signature' markers galectin-9 (dermatomyositis) and CCL4, CCL18, CXCL9, fetuin, fibronectin, galectin-1 and TSP-1 (EF). In LoS, CCL18, CXCL9 and CXCL10 were subtly increased. Furthermore, dermatomyositis and EF shared upregulation of markers related to interferon (CCL2, CXCL10), endothelial activation (VCAM-1), inhibition of angiogenesis (angiopoietin-2, sVEGFR-1) and inflammation/leucocyte chemo-attraction (CCL19, CXCL13, IL-18, YKL-40), as well as disturbance of the Angiopoietin-Tie receptor system and VEGF-VEGFR system. These profiles were related to disease activity, and largely normalized during treatment. However, a subgroup of CICTD patients showed continued elevation of CXCL10, CXCL13, galectin-9, IL-18, TNFR2, VCAM-1, and/or YKL-40 during clinically inactive disease, possibly indicating subclinical interferon-driven inflammation and/or endothelial dysfunction.
Conclusion:
CICTD-specific biomarker profiles revealed an anti-angiogenic, interferon-driven environment during active disease, with incomplete normalization under treatment. This warrants further investigation into monitoring of vascular biomarkers during clinical follow-up, or targeted interventions to minimize cardiovascular risk in the long term.
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