Haematopoietic and endothelial progenitor cells are deficient in quiescent systemic lupus erythematosus.
BACKGROUND
Systemic lupus erythematosus (SLE) is associated with a high prevalence of cardiovascular disease. Circulating endothelial progenitor cells (EPCs) contribute to vascular regeneration and repair, thereby protecting against atherosclerotic disease. EPCs are derived from CD34+ haematopoietic stem cells (HSCs), which have an increased propensity for apoptosis in the bone marrow of patients with SLE.


OBJECTIVE
To determine whether circulating HSCs and EPCs are reduced in SLE, contributing to an increased cardiovascular risk.


METHODS
Progenitor cells were sampled from 15 female patients with SLE in prolonged clinical remission from their disease and 15 matched healthy controls. HSC and CD34+KDR+ EPCs were quantified by flow cytometry. Annexin V staining was used to identify apoptotic cells.


RESULTS
Patients with SLE had reduced levels of circulating CD34+ HSCs and CD34+KDR+ EPCs, associated with increased HSC apoptosis. Compared with controls, the fraction of HSCs that could be identified as EPCs was higher in patients with SLE, consistent with a primary defect of HSCs. EPC outgrowth from mononuclear cells, which depends mainly on CD34- cells, was unaffected.


CONCLUSIONS
Patients with SLE have lower levels of circulating HSCs and EPCs, even during clinical remission. The data suggest that increased HSC apoptosis is the underlying cause for this depletion. These observations indicate that progenitor cell-mediated endogenous vascular repair is impaired in SLE, which may contribute to the accelerated development of atherosclerosis.
Westerweel
Peter E
PE
Department of Vascular Medicine, F02.126, University Medical Centre Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
Luijten
Remco K M A C
RK
Hoefer
Imo E
IE
Koomans
Hein A
HA
Derksen
Ronald H W M
RH
Verhaar
Marianne C
MC
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D018952:Antigens, CD34 / Q000502:physiology; D017209:Apoptosis / Q000502:physiology; D001158:Arteries / Q000503:physiopathology; D001772:Blood Cell Count; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000473:pathology*; D005260:Female; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D006801:Humans; D007963:Leukocytes, Mononuclear; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000503:physiopathology; D011241:Prednisone / Q000627:therapeutic use
D000893:Anti-Inflammatory Agents; D018952:Antigens, CD34; D011241:Prednisone