Ablin Jacob N, Boguslavski Viktoria, Aloush Valerie, Elkayam Ori, Paran Daphna, Caspi Dan, George Jacob
Department of Rheumatology, Tel-Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Life Sci. 2006 Nov 17;79(25):2364-9. doi: 10.1016/j.lfs.2006.07.035. Epub 2006 Aug 5.
Rheumatoid arthritis (RA) is associated with increased cardiovascular morbidity and mortality, which may be attenuated by anti-inflammatory treatment. Endothelial progenitor cells (EPCs) have the ability to differentiate into mature endothelium and have a potentially reparative role protecting against ischemia and atherosclerosis.
To investigate the effect of treatment with infliximab on the number and functional capacity of endothelial progenitor cells (EPCs) in patients with RA, as a possible mechanism for reducing cardiovascular morbidity in this disorder.
Active seropositive RA patients (N = 14) considered candidates for starting infliximab treatment, were recruited. Assessment, based on DAS-28, was performed before treatment and 14 days later. Peripheral blood mononuclear cells were isolated and EPC numbers evaluated by the colony-forming unit (CFU) method. Endothelial phenotyping of CFU was performed by immunofluorescence employing antibodies to Tie-2 VEGF-receptor 2, and CD31. EPC Functional properties were evaluated by fibronectin adherance.
A significant 33.4% increase (p < 0.001) in EPC levels was observed after infliximab. A 60% increase was noted in the EPC differentiation scale, (p < 0.002) while a 37.6% increase was observed in mean EPC adhesion (p < 0.001). These changes were associated with a 17.5% decrease in the DAS-28 (p < 0.0001). A significant correlation was observed between the clinical response, reflected by changes in DAS-28 and the degree of increase in EPC CFUs.
A single dose of infliximab improved the number and functional properties of EPCs, in parallel with an early clinical effect, suggesting a possible mechanism by which anti-inflammatory treatment may reduce cardiovascular risk in RA patients.
类风湿性关节炎（RA）与心血管疾病发病率和死亡率增加相关，抗炎治疗可能会减轻这种情况。内皮祖细胞（EPCs）有分化为成熟内皮的能力，并在预防缺血和动脉粥样硬化方面具有潜在的修复作用。
研究英夫利昔单抗治疗对RA患者内皮祖细胞（EPCs）数量和功能能力的影响，作为降低该疾病心血管发病率的一种可能机制。
招募了14名被认为适合开始英夫利昔单抗治疗的活动性血清阳性RA患者。在治疗前和14天后基于疾病活动评分28（DAS-28）进行评估。分离外周血单个核细胞，通过集落形成单位（CFU）法评估EPC数量。采用针对Tie-2、血管内皮生长因子受体2（VEGF-receptor 2）和CD31的抗体，通过免疫荧光对CFU进行内皮细胞表型分析。通过纤连蛋白黏附评估EPC的功能特性。
英夫利昔单抗治疗后，EPC水平显著增加33.4%（p < 0.001）。EPC分化程度增加60%（p < 0.002），同时平均EPC黏附增加37.6%（p < 0.001）。这些变化与DAS-28降低17.5%相关（p < 0.0001）。由DAS-28变化反映的临床反应与EPC CFU增加程度之间存在显著相关性。
单剂量英夫利昔单抗改善了EPC的数量和功能特性，同时产生早期临床效果，提示抗炎治疗可能降低RA患者心血管风险的一种可能机制。
