1. Biomarker profiles of endothelial activation and dysfunction in rare systemic autoimmune diseases: implications for cardiovascular risk.
- Author
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Wienke J, Mertens JS, Garcia S, Lim J, Wijngaarde CA, Yeo JG, Meyer A, van den Hoogen LL, Tekstra J, Hoogendijk JE, Otten HG, Fritsch-Stork RDE, de Jager W, Seyger MMB, Thurlings RM, de Jong EMGJ, van der Kooi AJ, van der Pol WL, Arkachaisri T, Radstake TRDJ, van Royen-Kerkhof A, and van Wijk F
- Subjects
- Autoimmunity, Chemokine CXCL10 blood, Chemokine CXCL13 blood, Female, Galectins blood, Heart Disease Risk Factors, Humans, Male, Middle Aged, Monitoring, Immunologic methods, Netherlands, Patient Acuity, Receptors, Tumor Necrosis Factor, Type II blood, Vascular Cell Adhesion Molecule-1 blood, Biomarkers blood, Dermatomyositis blood, Dermatomyositis diagnosis, Endothelium, Vascular immunology, Eosinophilia blood, Eosinophilia diagnosis, Fasciitis blood, Fasciitis diagnosis, Scleroderma, Localized blood, Scleroderma, Localized diagnosis
- Abstract
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., (Published by Oxford University Press on behalf of the British Society for Rheumatology 2020.)
- Published
- 2021
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