title: Endothelial progenitor cells are differentially impaired in ANCA-associated vasculitis compared to healthy controls.
abstract: Endothelial progenitor cells (EPC) are of major importance in vascular repair under healthy circumstances. Vascular injury in need of repair occurs frequently in ANCA-associated vasculitis (AAV). A specialized T cell subset enhancing EPC function and differentiation has recently been described. These angiogenic T cells (Tang) may have an important impact on the vascular repair process. Therefore, the aim of our study was to investigate EPC and Tang in AAV.
  
  
  
  Fifty-three patients suffering from AAV and 29 healthy controls (HC) were enrolled in our study. Forty-four patients were in remission, nine patients were in active state of disease. Patients were either untreated or were under monotherapy with low-dose steroids (max. 5 mg/day) at the time of sampling. Circulating EPC and Tang were determined by flow cytometry (FACS). The functional capacity of EPC was assessed by established cell culture methods.
  
  
  
  Circulating EPC were significantly decreased in AAV as compared to HC. The capacity of EPC to differentiate and proliferate was differentially impaired in patients as compared to HC. The outgrowth of endothelial colony-forming cells (ECFC) was severely decreased in patients whereas colony-forming units-endothelial cell (CFU-EC) outgrowth was unaffected. ECFC and CFU-EC differentiation was strictly T cell-dependent. Patients with a relapsing disease course had an impaired ECFC outgrowth and expansion of Tang as compared to patients with a stable, nonrelapsing disease.
  
  
  
  The differentiation process of EPC is impaired in AAV. This may favor insufficient vascular repair promoting a relapsing disease course. Finally, these factors may explain a higher cardiovascular morbidity as has been previously documented in AAV.
authors.affiliation: Immunology, Maastricht University, PO Box 5800, 6202 AZ, Maastricht, The Netherlands.|Department of Nephrology, University Duisburg-Essen, University Hospital Essen, Essen, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Wilde
authors.affiliation: Immunology, Maastricht University, PO Box 5800, 6202 AZ, Maastricht, The Netherlands.|Department of Neurology, University Hospital Maastricht, Maastricht, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Mertens
authors.affiliation: Immunology, Maastricht University, PO Box 5800, 6202 AZ, Maastricht, The Netherlands.
authors.forename: S J
authors.initials: SJ
authors.lastname: Arends
authors.affiliation: Immunology, Maastricht University, PO Box 5800, 6202 AZ, Maastricht, The Netherlands.|Department of Neurology, University Hospital Maastricht, Maastricht, The Netherlands.
authors.forename: R P
authors.initials: RP
authors.lastname: Rouhl
authors.affiliation: Immunology, Maastricht University, PO Box 5800, 6202 AZ, Maastricht, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Bijleveld
authors.affiliation: Immunology, Maastricht University, PO Box 5800, 6202 AZ, Maastricht, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Huitema
authors.affiliation: Immunology, Maastricht University, PO Box 5800, 6202 AZ, Maastricht, The Netherlands.
authors.forename: S A
authors.initials: SA
authors.lastname: Timmermans
authors.affiliation: Central Diagnostic Laboratory, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Damoiseaux
authors.affiliation: Department of Nephrology, University Duisburg-Essen, University Hospital Essen, Essen, Germany.|Department of Infectious Diseases, University Duisburg-Essen, University Hospital Essen, Essen, Germany.
authors.forename: O
authors.initials: O
authors.lastname: Witzke
authors.affiliation: Immunology, Maastricht University, PO Box 5800, 6202 AZ, Maastricht, The Netherlands.
authors.forename: A M
authors.initials: AM
authors.lastname: Duijvestijn
authors.affiliation: Immunology, Maastricht University, PO Box 5800, 6202 AZ, Maastricht, The Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: van Paassen
authors.affiliation: Department of Neurology, University Hospital Maastricht, Maastricht, The Netherlands.
authors.forename: R J
authors.initials: RJ
authors.lastname: van Oostenbrugge
authors.affiliation: Immunology, Maastricht University, PO Box 5800, 6202 AZ, Maastricht, The Netherlands. jw.cohentervaert@maastrichtuniversity.nl.
authors.forename: J W
authors.initials: JW
authors.lastname: Cohen Tervaert
mesh_terms: D000328:Adult; D000368:Aged; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000473:pathology*; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D066026:Endothelial Progenitor Cells / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000166:cytology
keywords: Autoantibodies; Endothelial progenitor cells; Vasculitis