Pingiotti Elisa, Cipriani Paola, Marrelli Alessandra, Liakouli Vasiliki, Fratini Simona, Penco Maria, Giacomelli Roberto
Department of Internal Medicine and Public Health, University of L'Aquila, Via Vetoio, Coppito, L'Aquila 67100, Italy.
Ann N Y Acad Sci. 2007 Jun;1107:32-41. doi: 10.1196/annals.1381.004.
Rheumatoid arthritis (RA) is associated with accelerated atherosclerosis. Fractalkine, a CX3C/chemokine (CX3CL1), mediates monocytes-macrophage infiltration in activated endothelium, suggesting its specific role in atherosclerosis-related inflammation. In this study, we evaluate the following in early RA patients: the expression of fractalkine receptor (CX3CR1) on CD4+/CD28- T cells, a subset involved in atherosclerotic infiltration; the correlation between this subset and validated markers of early atherosclerosis. CD4+ T cells were isolated by immunomagnetics beads in 50 early RA patients and 26 healthy controls (HC). After isolation, CD4+/CD28-/CX3CR1+ T lymphocytes were assessed by FACS analysis. Endothelial dysfunction was evaluated by both carotid intima-media thickness (IMT) and flow-mediated vasodilation (FMV). We observed: a higher expansion of CD4+/CD28- subset in RA patients when compared to HC (7.7%, 5.15-9.7 vs. 0.7%, 0.2-1.5, P < 0.01; respectively); this expansion directly correlated with increased IMT (0.91 mm, 0.5-1.3 vs. 0.7 mm, 0.2-1, P < 0.01; RA vs. C, respectively) and inversely correlated with FMV (3.5%, 1.7-7 vs. 9%, 3.5-11, P < 0.01; RA vs. C, respectively); the large majority of CD4+/CD28-, in RA, coexpressed CX3CR1 (93%, 67-99 vs. 30%, 10-48, P < 0.01; RA vs. C, respectively); this expansion significantly correlated with both the parameters of premature vascular damage and DAS 28. Our data suggest that CX3CL1/CX3CR1 axis might play a role in the induction and development of the endothelial dysfunction during RA.
类风湿关节炎(RA)与动脉粥样硬化加速有关。趋化因子,一种CX3C趋化因子(CX3CL1),介导单核细胞 - 巨噬细胞浸润活化的内皮细胞,提示其在动脉粥样硬化相关炎症中具有特定作用。在本研究中,我们评估了早期RA患者的以下情况:参与动脉粥样硬化浸润的CD4 + / CD28 - T细胞亚群上趋化因子受体(CX3CR1)的表达;该亚群与早期动脉粥样硬化验证标志物之间的相关性。通过免疫磁珠从50例早期RA患者和26例健康对照(HC)中分离CD4 + T细胞。分离后,通过流式细胞术分析评估CD4 + / CD28 - / CX3CR1 + T淋巴细胞。通过颈动脉内膜中层厚度(IMT)和血流介导的血管舒张(FMV)评估内皮功能障碍。我们观察到:与HC相比,RA患者中CD4 + / CD28 - 亚群的扩增更高(分别为7.7%,5.15 - 9.7对0.7%,0.2 - 1.5,P <0.01);这种扩增与IMT增加直接相关(分别为0.91mm,0.5 - 1.3对0.7mm,0.2 - 1,P <0.01;RA对C),与FMV呈负相关(分别为3.5%,1.7 - 7对9%,3.5 - 11,P <0.01;RA对C);在RA中绝大多数CD4 + / CD28 - 共表达CX3CR1(分别为93%,67 - 99对30%,10 - 48,P <0.01;RA对C);这种扩增与血管过早损伤参数和DAS 28均显著相关。我们的数据表明,CX3CL1 / CX3CR1轴可能在RA期间内皮功能障碍的诱导和发展中起作用。