Markers of endothelial glycocalyx dysfunction in Clarkson disease.

Autor: Xie Z; Lung and Vascular Inflammation Section, Laboratory of Allergic Diseases, National, Institute of Allergy and Infectious Diseases/National Institutes of Health, (NIAID/NIH), 10 Center Drive, Room 11N238A, Bethesda, MD, 20892, USA., Børset M; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.; Department of Immunology and Transfusion Medicine, St. Olav's University, Hospital, Trondheim, Norway., Svéen K; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway., Bøe OW; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway., Chan EC; Lung and Vascular Inflammation Section, Laboratory of Allergic Diseases, National, Institute of Allergy and Infectious Diseases/National Institutes of Health, (NIAID/NIH), 10 Center Drive, Room 11N238A, Bethesda, MD, 20892, USA., Lack JB; NIAID Collaborative Bioinformatics Resource, NIAID/NIH, Health, Bethesda, MD, 20892, USA., Hornick KM; NIAID Collaborative Bioinformatics Resource, NIAID/NIH, Health, Bethesda, MD, 20892, USA., Verlicchi F; Transfusion Medicine Faenza-Lugo, Transfusion Service Ravenna, Romagna Health Unit, Ravenna, Italy., Eisch AR; Lung and Vascular Inflammation Section, Laboratory of Allergic Diseases, National, Institute of Allergy and Infectious Diseases/National Institutes of Health, (NIAID/NIH), 10 Center Drive, Room 11N238A, Bethesda, MD, 20892, USA., Melchio R; Department of Internal Medicine, Santa Croce E Carle' Hospital, Via Michele Coppino 26, Cuneo, Italy., Dudek AZ; HealthPartners Neuroscience Center, St. Paul, MN, USA., Druey KM; Lung and Vascular Inflammation Section, Laboratory of Allergic Diseases, National, Institute of Allergy and Infectious Diseases/National Institutes of Health, (NIAID/NIH), 10 Center Drive, Room 11N238A, Bethesda, MD, 20892, USA. kdruey@niaid.nih.gov.
Jazyk: angličtina
Zdroj: Journal of translational medicine [J Transl Med] 2022 Aug 29; Vol. 20 (1), pp. 380. Date of Electronic Publication: 2022 Aug 29.
DOI: 10.1186/s12967-022-03587-1
Abstrakt: Background: Clarkson disease (monoclonal gammopathy-associated idiopathic systemic capillary leak syndrome, ISCLS) is a rare idiopathic condition marked by transient, relapsing-remitting episodes of systemic microvascular hyper-permeability, which liberates plasma fluid and macromolecules into the peripheral tissues. This pathology manifests clinically as the abrupt onset of hypotensive shock, hemoconcentration, and hypoalbuminemia.
Methods: We analysed endothelial glycocalyx (eGCX)-related markers in plasma from patients with ISCLS during acute disease flares and convalescence by ELISA and comprehensive proteomic profiling. We evaluated eGCX-related components and gene expression in cultured endothelial cells using RNA-sequencing, real-time PCR, and fluorescence staining.
Results: Serum levels of eGCX-related core components including hyaluronic acid (HA) and the core proteoglycan soluble syndecan-1 (sCD138) were elevated at baseline and during acute ISCLS flares. Serial measurements demonstrated that sCD138 levels peaked during the recovery (post-leak) phase of the illness. Proteomic analysis of matched acute and convalescent ISCLS plasma revealed increased abundance of eGCX-related proteins, including glypicans, thrombospondin-1 (TSP-1), and eGCX-degrading enzymes in acute compared to remission plasma. Abundance of endothelial cell damage markers did not differ in acute and baseline plasma. Expression of several eGCX-related genes and surface carbohydrate content in endothelial cells from patients with ISCLS did not differ significantly from that observed in healthy control cells.
Conclusions: eGCX dysfunction, but not endothelial injury, may contribute to clinical symptoms of acute ISCLS. Serum levels of of eGCX components including sCD138 may be measured during acute episodes of ISCLS to monitor clinical status and therapeutic responses.
(© 2022. The Author(s).)
Databáze: MEDLINE
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