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. METHODS AND 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.

Ankylosing spondylitis, psoriatic arthritis, and reactive arthritis show increased bone resorption, but differ with regard to bone formation.

OBJECTIVE: To test if markers of bone metabolism are altered in patients with seronegative spondyloarthropathies (SSpA). METHODS: We studied biochemical markers of bone resorption and bone formation, osteoprotegerin (OPG), and bone mineral density (BMD) in patients with psoriatic arthritis (PsA), ankylosing spondylitis (AS), and reactive arthritis (ReA) and healthy volunteers. RESULTS: The bone resorption markers urinary deoxypyridinoline and crosslinked telopeptide of collagen-I were significantly increased in patients with AS, PsA, and ReA; in PsA they correlated with the acute phase response (C-reactive protein and erythrocyte sedimentation rate). The bone formation markers were divergent: bone-specific alkaline phosphatase was increased in PsA, but not in AS or ReA. Osteocalcin levels were only elevated in AS. Serum levels of OPG were significantly increased in both AS and PsA. Dual energy x-ray absorptiometry (DEXA) measurements of lumbar spine and femoral neck revealed osteopenia in patients with AS, whereas the DEXA distribution was within normal range in PsA. CONCLUSION: Our data indicate high and, particularly in AS, unbalanced bone turnover in SSpA, consistent with the decrease in BMD found in patients with AS.