Abstract

摘要

Background:

背景：

Germinal center kinase-like kinase (GLK, also termed MAP4K3), a member of the MAP4K family, may regulate gene transcription, apoptosis and immune inflammation in response to extracellular signals. The enhanced expression of GLK has been shown to correspond with disease severity in patients with systemic lupus erythematosus. We investigated the role of GLK in the pathogenesis of adult-onset Still’s disease, which shares some similar clinical characteristics with systemic lupus erythematosus.

生发中心激酶样激酶（GLK，也称为MAP4K3），MAP4K家族的一员，可以调节基因转录、细胞凋亡和免疫炎症，并且对细胞外信号有响应。GLK的表达增强已被证明与系统性红斑狼疮患者的疾病严重程度相符。我们调查了GLK在成人Still病发病机制中的作用，成人Still病具有与系统性红斑狼疮相似的一些临床特点。

Methods:

方法：

The frequencies of circulating GLK-expressing T-cells in 24 patients with active adult-onset Still’s disease and 12 healthy controls were determined by flow cytometry analysis. The expression levels of GLK proteins and transcripts were evaluated in peripheral blood mononuclear cells by immunoblotting and quantitative PCR. Serum levels of T helper (Th)17-related cytokines, including IL-1b, IL-6, IL-17 and TNF-a, were measured by ELISA.

在24名活跃的成人Still病患者和12名健康对照者中，采用流式细胞仪分析测定循环GLK表达T细胞的频率。在外周血单核细胞中通过免疫印迹和定量PCR对GLK蛋白质和转录物的表达水平进行了评估。采用ELISA法测定T辅助因子（Th）17相关的细胞因子，包括IL -1β 、IL-6 、IL-17和TNF -α的血清水平。

Results:

结果：

Significantly higher median frequencies of circulating GLK-expressing T-cells were observed in patients with adult-onset Still’s disease (31.85%) than in healthy volunteers (8.93%, P <0.001). The relative expression levels of GLK proteins and transcripts were also significantly higher in patients with adult-onset Still’s disease (median, 1.74 and 2.35, respectively) compared with those in healthy controls (0.66 and 0.92, respectively, both P <0.001). The disease activity scores were positively correlated with the frequencies of circulating GLK-expressing T-cells (r = 0.599, P <0.005) and the levels of GLK proteins (r = 0.435, P <0.05) or GLK transcripts (r = 0.452, P <0.05) in patients with adult-onset Still’s disease. Among the examined Th17-related cytokines, elevated levels of serum IL-6 and IL-17 were positively correlated with the frequencies of circulating GLK-expressing T-cells and the levels of GLK proteins as well as transcripts in patients with adult-onset Still’s disease. GLK expression levels decreased significantly after effective therapy in these patients.

与健康志愿者（8.93％，P <0.001）相比，在成人Still病患者中可以观察到显著较高的循环GLK表达T细胞的平均频率（31.85％）。与那些健康对照组相比（0.66和0.92，P < 0.001），成人Still病患者的GLK的蛋白质和转录物的相对表达水平也显著较高（中间值，分别为1.74和2.35）。在成人Still病患者中，疾病活动评分与循环GLK表达T细胞的频率（r = 0.599，P <0.005）和GLK蛋白水平（r = 0.435，P <0.05）或GLK转录物水平（r = 0.452，P <0.05）相关。在检查过的Th17相关的细胞因子中，成人Still病患者中血清IL-6和IL-17水平升高与循环GLK -表达的T-细胞频率和GLK蛋白质和转录物水平相关。这些患者在得到有效治疗后GLK表达水平显著下降。

Conclusions:

结论：

Elevated expression levels of GLK and their positive correlation with disease activity in patients with adult-onset Still’s disease indicate that GLK may be involved in the pathogenesis and act as a novel activity biomarker of this disease.

在成人Still病中，GLK表达水平的升高及其与患者的疾病活动指数呈正相关表明GLK可能参与该疾病的发病机制，并且作为该疾病的一种新的活性生物标志物。