Baldini Mattia, Maugeri Norma, Ramirez Giuseppe A, Giacomassi Chiara, Castiglioni Alessandra, Prieto-González Sergio, Corbera-Bellalta Marc, Di Comite Gabriele, Papa Ilenia, Dell'antonio Giacomo, Ammirati Enrico, Cuccovillo Ivan, Vecchio Viviana, Mantovani Alberto, Rovere-Querini Patrizia, Sabbadini Maria Grazia, Cid Maria C, Manfredi Angelo A
Istituto Scientifico San Raffaele and Università Vita-Salute San Raffaele, Milan, Italy.
Arthritis Rheum. 2012 Mar;64(3):854-65. doi: 10.1002/art.33411.
To assess local expression and plasma levels of pentraxin 3 (PTX3) in patients with giant cell arteritis (GCA).
Plasma and serum samples were obtained from 75 patients with GCA (20 of whom had experienced optic nerve ischemia in the previous 3 weeks and 24 of whom had experienced symptom onset in the previous 6 months and had no history of optic nerve ischemia) and 63 controls (35 age-matched healthy subjects, 15 patients with rheumatoid arthritis, and 13 patients with chronic stable angina). In 9 patients in whom GCA was recently diagnosed, circulating levels of interleukin-1β (IL-1β), IL-2, IL-4, IL-6, IL-7, IL-8, IL-10, IL-12p70, CCL2/monocyte chemotactic protein 1, CCL3/macrophage inflammatory protein 1α (MIP-1α), CCL4/MIP-1β, CCL11/eotaxin, CXCL9/monokine induced by interferon-γ, CXCL10/interferon-γ-inducible 10-kd protein, tumor necrosis factor α (TNFα), interferon-γ, vascular endothelial growth factor (VEGF), granulocyte-macrophage colony-stimulating factor, and FasL were measured via a multiplexed cytometric assay. PTX3 and VEGF concentrations were assessed by enzyme-linked immunosorbent assay. PTX3 and CD68 expression were determined by immunohistochemistry and immunofluorescence on temporal artery samples.
GCA patients with very recent optic nerve ischemia had significantly higher PTX3 and VEGF levels compared to other GCA patients and controls. GCA patients with a disease duration of <6 months had significantly higher PTX3 levels compared to other GCA patients and controls. Immunohistochemistry revealed selective PTX3 expression in the wall of inflamed arteries.
Our findings indicate that local expression of PTX3 is a feature of vascular inflammation in GCA; elevated circulating levels of PTX3 identify patients with very recent optic nerve ischemia or a recent diagnosis. Optic nerve ischemia is also associated with increased circulating VEGF levels.
评估巨细胞动脉炎（GCA）患者中五聚体3（PTX3）的局部表达及血浆水平。
采集了75例GCA患者（其中20例在过去3周内发生过视神经缺血，24例在过去6个月内出现症状且无视神经缺血病史）和63例对照者（35例年龄匹配的健康受试者、15例类风湿关节炎患者和13例慢性稳定型心绞痛患者）的血浆和血清样本。在9例近期诊断为GCA的患者中，通过多重细胞检测法测定循环中的白细胞介素-1β（IL-1β）、IL-2、IL-4、IL-6、IL-7、IL-8、IL-10、IL-12p70、CCL2/单核细胞趋化蛋白1、CCL3/巨噬细胞炎性蛋白1α（MIP-1α）、CCL4/MIP-1β、CCL11/嗜酸性粒细胞趋化因子、CXCL9/γ干扰素诱导的单核因子、CXCL10/γ干扰素诱导的10-kD蛋白、肿瘤坏死因子α（TNFα）、γ干扰素、血管内皮生长因子（VEGF）、粒细胞-巨噬细胞集落刺激因子和FasL水平。通过酶联免疫吸附测定法评估PTX3和VEGF浓度。通过对颞动脉样本进行免疫组织化学和免疫荧光测定PTX3和CD68表达。
与其他GCA患者及对照者相比，近期发生视神经缺血的GCA患者的PTX3和VEGF水平显著更高。病程<6个月的GCA患者的PTX3水平显著高于其他GCA患者及对照者。免疫组织化学显示PTX3在炎症动脉壁中有选择性表达。
我们的研究结果表明，PTX3的局部表达是GCA血管炎症的一个特征；PTX3循环水平升高可识别近期发生视神经缺血或近期确诊的患者。视神经缺血还与循环VEGF水平升高有关。
