George Jacob, Matucci-Cerinic Marco, Bar Iris, Shimoni Sara
Heart Center, Kaplan Medical Center, Rehovot, Affiliated to the Hebrew University, Jerusalem, Israel.
Department of Experimental and Clinical Medicine, Division of Rheumatology AOUC, University of Florence, Florence, Italy.
PLoS One. 2014 Jun 19;9(6):e97836. doi: 10.1371/journal.pone.0097836. eCollection 2014.
Endothelial progenitor cells (EPC) are committed to transform into EC promoting vasculogenic ischemic repair. Anti-endothelial cells (AECA) have been described in various disorders with an associated vascular damage. Herein, we explored a novel circulating population of IgG reactive with EPC, in patients with differential risk profile for atherosclerotic vascular disease.
A novel cyto-ELISA system was established where the coated cells were late outgrowth EPC. Levels of anti-EPC antibodies were determined in 100 subjects and differential risk score for atherosclerosis, as well as to circulating EPC levels and the inflammatory markers IL-6 and C-reactive protein. To study endothelial cell (EC) activating properties, sera were tested for their ability to induce VCAM-1 expression in a cell ELISA system. Detectable levels of anti-EPC antibodies, that correlated with age, Framingham risk score and CRP concentrations but did not associate with levels of LDL, HDL, hypertension or diabetes, were detected. Anti-EPC antibodies were distinct from EC binding antibodies as shown by competitive inhibition studies, and have been positively correlated with the extent of EC activation manifested by in vitro VCAM-1 expression.
This is the first study showing a newly defined subgroup of self-antibodies binding EPC and associating positively with the Framingham risk score. Further studies are required to characterize and test this interesting subset of EPC binding autoantibodies and their potential significance.
内皮祖细胞（EPC）致力于转化为内皮细胞，促进血管生成性缺血修复。抗内皮细胞抗体（AECA）已在各种伴有血管损伤的疾病中被描述。在此，我们在具有不同动脉粥样硬化血管疾病风险特征的患者中，探索了一种与EPC反应的新型循环IgG群体。
建立了一种新型细胞酶联免疫吸附测定系统，其中包被细胞为晚期贴壁EPC。测定了100名受试者中抗EPC抗体的水平、动脉粥样硬化的差异风险评分，以及循环EPC水平和炎症标志物白细胞介素-6（IL-6）和C反应蛋白。为研究内皮细胞（EC）激活特性，在细胞酶联免疫吸附测定系统中检测血清诱导血管细胞黏附分子-1（VCAM-1）表达的能力。检测到可检测水平的抗EPC抗体，其与年龄、弗雷明汉风险评分和CRP浓度相关，但与低密度脂蛋白（LDL）、高密度脂蛋白（HDL）水平、高血压或糖尿病无关。竞争性抑制研究表明，抗EPC抗体与EC结合抗体不同，并且与体外VCAM-1表达所表现的EC激活程度呈正相关。
这是第一项显示新定义的与EPC结合且与弗雷明汉风险评分呈正相关的自身抗体亚组的研究。需要进一步研究来表征和测试这一有趣的EPC结合自身抗体子集及其潜在意义。
