Markers of endothelial glycocalyx dysfunction in Clarkson disease
Abstract 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 in...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-08-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-022-03587-1 |
| _version_ | 1828352017156800512 |
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| author | Zhihui Xie Magne Børset Kjell Svéen Ole Wilhelm Bøe Eunice C. Chan Justin B. Lack Katherine M. Hornick Franco Verlicchi A. Robin Eisch Remo Melchio Arkadiusz Z. Dudek Kirk M. Druey |
| author_facet | Zhihui Xie Magne Børset Kjell Svéen Ole Wilhelm Bøe Eunice C. Chan Justin B. Lack Katherine M. Hornick Franco Verlicchi A. Robin Eisch Remo Melchio Arkadiusz Z. Dudek Kirk M. Druey |
| author_sort | Zhihui Xie |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-14T01:47:46Z |
| format | Article |
| id | doaj.art-80df63f871344a43b4138ca07a22ab31 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-14T01:47:46Z |
| publishDate | 2022-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-80df63f871344a43b4138ca07a22ab312022-12-22T02:19:27ZengBMCJournal of Translational Medicine1479-58762022-08-0120111010.1186/s12967-022-03587-1Markers of endothelial glycocalyx dysfunction in Clarkson diseaseZhihui Xie0Magne Børset1Kjell Svéen2Ole Wilhelm Bøe3Eunice C. Chan4Justin B. Lack5Katherine M. Hornick6Franco Verlicchi7A. Robin Eisch8Remo Melchio9Arkadiusz Z. Dudek10Kirk M. Druey11Lung and Vascular Inflammation Section, Laboratory of Allergic Diseases, National, Institute of Allergy and Infectious Diseases/National Institutes of Health, (NIAID/NIH)Department of Clinical and Molecular Medicine, Norwegian University of Science and TechnologyDepartment of Clinical and Molecular Medicine, Norwegian University of Science and TechnologyDepartment of Clinical and Molecular Medicine, Norwegian University of Science and TechnologyLung and Vascular Inflammation Section, Laboratory of Allergic Diseases, National, Institute of Allergy and Infectious Diseases/National Institutes of Health, (NIAID/NIH)NIAID Collaborative Bioinformatics Resource, NIAID/NIH, HealthNIAID Collaborative Bioinformatics Resource, NIAID/NIH, HealthTransfusion Medicine Faenza-Lugo, Transfusion Service Ravenna, Romagna Health UnitLung and Vascular Inflammation Section, Laboratory of Allergic Diseases, National, Institute of Allergy and Infectious Diseases/National Institutes of Health, (NIAID/NIH)Department of Internal Medicine, Santa Croce E Carle’ HospitalHealthPartners Neuroscience CenterLung and Vascular Inflammation Section, Laboratory of Allergic Diseases, National, Institute of Allergy and Infectious Diseases/National Institutes of Health, (NIAID/NIH)Abstract 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.https://doi.org/10.1186/s12967-022-03587-1Capillary leakEndotheliumGlyocalcyx |
| spellingShingle | Zhihui Xie Magne Børset Kjell Svéen Ole Wilhelm Bøe Eunice C. Chan Justin B. Lack Katherine M. Hornick Franco Verlicchi A. Robin Eisch Remo Melchio Arkadiusz Z. Dudek Kirk M. Druey Markers of endothelial glycocalyx dysfunction in Clarkson disease Journal of Translational Medicine Capillary leak Endothelium Glyocalcyx |
| title | Markers of endothelial glycocalyx dysfunction in Clarkson disease |
| title_full | Markers of endothelial glycocalyx dysfunction in Clarkson disease |
| title_fullStr | Markers of endothelial glycocalyx dysfunction in Clarkson disease |
| title_full_unstemmed | Markers of endothelial glycocalyx dysfunction in Clarkson disease |
| title_short | Markers of endothelial glycocalyx dysfunction in Clarkson disease |
| title_sort | markers of endothelial glycocalyx dysfunction in clarkson disease |
| topic | Capillary leak Endothelium Glyocalcyx |
| url | https://doi.org/10.1186/s12967-022-03587-1 |
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