van Sleen Yannick, Sandovici Maria, Abdulahad Wayel H, Bijzet Johan, van der Geest Kornelis S M, Boots Annemieke M H, Brouwer Elisabeth
Vasculitis Expertise Center Groningen, Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Rheumatology (Oxford). 2019 Feb 25;58(8):1383-92. doi: 10.1093/rheumatology/kez034.
GCA, a systemic vasculitis, is characterized by an IL-6-dependent acute-phase response. This response is typically suppressed by treatment rendering CRP/ESR unreliable for monitoring vascular inflammation. Also, there are no accurate biomarkers predicting a non-favourable disease course. Here we investigated macrophage products and markers of angiogenesis as biomarkers for prognosis and monitoring of vascular inflammation.
Forty-one newly diagnosed, glucocorticoid-naive GCA patients were prospectively followed for relapses and glucocorticoid requirement for a median of 30 months (range 0-71). Serum markers at baseline and during follow-up were compared with 33 age-matched healthy controls and 13 infection controls. Concentrations of IL-6, serum amyloid A, soluble CD163, calprotectin, YKL-40, VEGF, angiopoietin-1 and -2 and sTie2 were determined by ELISA/Luminex assay.
Serum concentrations of all markers, but not angiopoietin-1, were elevated in GCA patients at baseline when compared with healthy controls. High VEGF (P = 0.0025) and angiopoietin-1 (P = 0.0174) and low YKL-40 (P = 0.0369) levels at baseline were predictive of a short time to glucocorticoid-free remission. Elevated angiopoietin-2 levels were associated with an imminent relapse during treatment (P < 0.05). IL-6 correlated strongly with acute-phase markers and soluble CD163 but not with markers of angiogenesis, YKL-40 or calprotectin. Glucocorticoid treatment down-modulated all markers except for calprotectin and YKL-40. Tissue expression of markers in temporal arteries was confirmed.
Markers of angiogenesis at baseline and during treatment predict GCA disease course, suggesting utility in patient stratification for glucocorticoid-sparing therapy. Calprotectin and YKL-40 are candidate markers for monitoring vessel wall inflammation.
巨细胞动脉炎（GCA）是一种系统性血管炎，其特征为依赖白细胞介素-6（IL-6）的急性期反应。这种反应通常会因治疗而受到抑制，使得C反应蛋白（CRP）/红细胞沉降率（ESR）在监测血管炎症时不可靠。此外，尚无准确的生物标志物可预测不良的疾病进程。在此，我们研究了巨噬细胞产物和血管生成标志物作为血管炎症预后和监测的生物标志物。
对41例新诊断、未使用过糖皮质激素的GCA患者进行前瞻性随访，观察复发情况和糖皮质激素需求，中位随访时间为30个月（范围0 - 71个月）。将基线期及随访期间的血清标志物与33例年龄匹配的健康对照者及13例感染对照者进行比较。采用酶联免疫吸附测定（ELISA）/Luminex检测法测定IL-6、血清淀粉样蛋白A、可溶性CD163、钙卫蛋白、YKL-40、血管内皮生长因子（VEGF）、血管生成素-1和 -2以及可溶性酪氨酸激酶内皮受体2（sTie2）的浓度。
与健康对照者相比，GCA患者在基线期时所有标志物（但血管生成素-1除外）的血清浓度均升高。基线期高VEGF水平（P = 0.0025）、血管生成素-1水平（P = 0.0174）及低YKL-40水平（P = 0.0369）可预测无糖皮质激素缓解的时间较短。血管生成素-2水平升高与治疗期间即将复发相关（P < 0.05）。IL-6与急性期标志物及可溶性CD163密切相关，但与血管生成标志物、YKL-40或钙卫蛋白无关。糖皮质激素治疗下调了除钙卫蛋白和YKL-40之外的所有标志物。颞动脉中标志物的组织表达得到证实。
基线期及治疗期间的血管生成标志物可预测GCA的疾病进程，提示其在糖皮质激素节省疗法的患者分层中具有实用价值。钙卫蛋白和YKL-40是监测血管壁炎症的候选标志物。
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