Vascular endothelial damage and repair in antineutrophil cytoplasmic antibody-associated vasculitis.
OBJECTIVE
Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is characterized by necrotizing vessel wall inflammation, paralleled by the detachment of endothelial cells. The repair of such endothelial defects is crucial for the maintenance of regular structure and function of the injured vessels. Bone marrow-derived endothelial progenitor cells (EPCs) are thought to play a pivotal role in the regeneration of damaged endothelium. The aim of this study was to investigate whether EPCs are involved in vascular repair in AAV.


METHODS
We assessed disease activity, CD34+ hematopoietic progenitor cells (HPCs) using flow cytometry, EPCs using an in vitro assay, and circulating endothelial cells (CECs) by immunomagnetic isolation from the peripheral blood of 31 patients with active AAV at 1, 3, and 6 months after the initiation of immunosuppressive therapy.


RESULTS
In patients with untreated active disease, HPC and EPC numbers were comparable with those in healthy control subjects (n = 64). With the induction of remission, the number of HPCs and EPCs increased significantly, from a median of 1.5 cells/microl (range 0.0-7.0) to a median of 3.2 cells/microl (range 0.76-9.2) (P < 0.001) and from a median of 261 cells/high-power field (range 171-643) to a median of 470 cells/high-power field (range 168-996) (P < 0.021), respectively. In contrast, the initially elevated number of CECs decreased significantly (P < 0.001). We observed no correlation between the number of HPCs or EPCs and the leukocyte count, the thrombocyte count, or kidney function.


CONCLUSIONS
In patients with AAV, the numbers of circulating CD34+ HPCs and EPCs increased significantly after the institution of immunosuppressive therapy and disease remission. This finding points to a role of circulating CD34+ HPCs and EPCs in endothelial repair in vasculitis. Targeted stimulation of these cells might represent a new possibility of improving vascular healing in AAV.
de Groot
K
K
Hannover Medical School, Hannover, Germany. kirsten@de-groot.de
Goldberg
C
C
Bahlmann
F H
FH
Woywodt
A
A
Haller
H
H
Fliser
D
D
Haubitz
M
M
D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology*; D018952:Antigens, CD34 / Q000378:metabolism; D042783:Endothelial Cells / Q000276:immunology / Q000473:pathology; D004730:Endothelium, Vascular / Q000276:immunology* / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D018189:Immunomagnetic Separation; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D009336:Necrosis; D016896:Treatment Outcome; D014657:Vasculitis / Q000188:drug therapy / Q000276:immunology / Q000473:pathology
D019268:Antibodies, Antineutrophil Cytoplasmic; D018952:Antigens, CD34; D007166:Immunosuppressive Agents