Depletion of endothelial progenitor cells in the peripheral blood of patients with rheumatoid arthritis.
BACKGROUND
Rheumatoid arthritis (RA) is characterized by increased cardiovascular morbidity and mortality that cannot be explained solely by traditional cardiovascular risk factors. Cardiovascular morbidity is related to disease activity and can be normalized by effective therapy. Because the quantity of endothelial progenitor cells (EPCs) in the peripheral blood is correlated inversely with cardiovascular risk, we studied whether such abnormalities could also be observed in patients with RA.


RESULTS
EPCs were determined in 52 RA patients and in 16 healthy referents (HRs) by fluorescence-activated cell-sorting (FACS) analysis. Patients were divided into groups characterized by active disease (n=36) and low disease activity (n=16). Cells that were positive by flow cytometry for CD34/KDR/AC133 within the lymphocyte population were characterized as EPCs. Furthermore, in subgroups of patients, circulating EPCs were also quantified by a colony-forming unit (CFU) and a circulating angiogenic cell (CAC) assay. EPCs were significantly decreased in RA patients suffering from active disease compared with those from HRs, as measured by FACS analysis (0.026+/-0.002% versus 0.045+/-0.008%, respectively, P<0.05), CFU assay (mean of 5+/-2 versus 18+/-5 CFU/well in HRs, P<0.05), and CAC assay (mean of 7+/-2 versus 52+/-16 positive cells/high-power field, P<0.005). In contrast, the frequency of circulating EPCs from patients with low disease activity was comparable to that of healthy individuals (0.052+/-0.006% by FACS analysis), CFU assay (10+/-5 CFU/well), and CAC assay (mean of 25+/-5 positive cells). Moreover, EPC quantities in peripheral blood were correlated inversely with disease activity as assessed by the disease activity score (r=-0.38, P<0.01).


CONCLUSIONS
Our observations indicate that active RA is associated with a depletion of circulating EPCs. This might be one of several factors contributing to the increased cardiovascular risk in RA.
Grisar
Johannes
J
Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria. johannes.grisar@meduniwien.ac.at
Aletaha
Daniel
D
Steiner
Carl W
CW
Kapral
Theresa
T
Steiner
Sabine
S
Seidinger
Daniela
D
Weigel
Günter
G
Schwarzinger
Ilse
I
Wolozcszuk
Wolfgang
W
Steiner
Günter
G
Smolen
Josef S
JS
D000071916:AC133 Antigen; D000368:Aged; D015703:Antigens, CD; D018952:Antigens, CD34 / Q000032:analysis; D000943:Antigens, Differentiation / Q000032:analysis; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000150:complications; D001327:Autoimmune Diseases / Q000097:blood*; D001772:Blood Cell Count; D002097:C-Reactive Protein / Q000032:analysis; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology; D003114:Colony-Forming Units Assay; D004198:Disease Susceptibility; D042783:Endothelial Cells / Q000166:cytology; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000097:blood; D005434:Flow Cytometry; D006023:Glycoproteins / Q000032:analysis; D006412:Hematopoietic Stem Cells / Q000737:chemistry; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D010455:Peptides / Q000032:analysis; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood; D012306:Risk; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis
D000071916:AC133 Antigen; D015703:Antigens, CD; D018952:Antigens, CD34; D000943:Antigens, Differentiation; D006023:Glycoproteins; D018950:Lipopolysaccharide Receptors; C000606023:PROM1 protein, human; D010455:Peptides; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D002097:C-Reactive Protein; D040301:Vascular Endothelial Growth Factor Receptor-2