Abstract
Histological findings in small-vessel vasculitis associated with antineutrophil cytoplasmic antibodies (ANCAs) suggest that damaged endothelial cells undergo necrosis and detachment from the basement membrane. We postulated that isolation of these cells from peripheral blood might provide a novel marker of the disease and elucidate pathogenetic events. 18 patients with active ANCA-associated vasculitis, 20 patients in remission, 20 healthy controls, 12 patients with infection, and 12 patients with glomerular disease not associated with ANCA were studied. Endothelial cells were isolated from peripheral blood by use of Dynabeads coated with antibodies against CD146, and were stained for von Willebrand factor (vWF), CD31, and Ulex Europaeus lectin 1 (UEA-1). Tissue-factor immunocytochemistry and assays for markers of apoptosis and necrosis were also done. Few circulating endothelial cells were seen in healthy controls (0-20 cells/mL, median 5 cells/mL), patients with infection (0-16 cells/mL, median 8 cells/mL), and patients with non-ANCA glomerulonephritis (0-21 cells/mL, median 4 cells/mL). By contrast, large numbers of circulating endothelial cells were detected in patients with active vasculitis (20-5700 cells/mL, median 136 cells/mL, p<0.0001 when compared with healthy controls). Cell numbers fell substantially during 6 months of successful immunosuppressive treatment among those with active disease. Patients in remission had moderately raised cell numbers (0-60 cells/mL, median 16 cells/mL). 84% of cells obtained from patients with active disease stained positive for annexin/propidium iodide and 86% stained tissue factor positive, indicating a necrotic and procoagulant phenotype. Circulating endothelial cells are a novel marker of active ANCA-associated small-vessel vasculitis. The clinical use of this tool and the pathogenic mechanisms leading to these findings require further investigation.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.