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眼内生物标志物鉴定在与幼年特发性关节炎相关的葡萄膜炎中。

Intraocular biomarker identification in uveitis associated with juvenile idiopathic arthritis.

机构信息

Department of Ophthalmology, University Medical Center Utrecht, Utrecht, The Netherlands.

出版信息

Invest Ophthalmol Vis Sci. 2013 May 1;54(5):3709-20. doi: 10.1167/iovs.12-10865.

DOI:10.1167/iovs.12-10865
PMID:23633652
Abstract

PURPOSE

To investigate the presence of biomarkers in aqueous humor (AH) from patients with uveitis associated with juvenile idiopathic arthritis (JIA).

METHODS

AH (N = 73) AND SERUM (N = 105) SAMPLES FROM 116 CHILDREN WERE ANALYZED USING SURFACE ENHANCED LASER DESORPTION/IONIZATION TIME OF FLIGHT MASS SPECTROMETRY (SELDI-TOF MS).

THE SAMPLES WERE DIVIDED INTO THE FOLLOWING GROUPS

JIA, silent chronic anterior uveitis (AU), other uveitis entities, and noninflammatory controls. Statistical biomarker identification was performed using the SELDI-ToF Biomarker Analysis Cluster Wizard followed by multivariate statistical analysis. Biochemical identification of biomarkers was performed by polyacrylamide gel protein separation, followed by liquid chromatography tandem mass spectrometry. ELISA was performed in a number of AH samples representing all four study groups.

RESULTS

In the JIA group, one AH protein peak at mass/charge (m/z) 13,762 had qualitative and quantitative differences in expression compared with the other uveitis entities and the controls, but not to the group of silent chronic AU. Its quantitative expression in AH of patients with JIA and other silent chronic AU was positively associated with uveitis activity. The protein at m/z 13,762 in AH was identified as transthyretin (TTR). The TTR concentration in AH differed significantly between the study groups (P = 0.006) with considerably higher TTR concentrations in JIA and silent chronic AU samples positive for m/z 13,762 than those of the other uveitis and control groups.

CONCLUSIONS

TTR is a potential intraocular biomarker of JIA- associated uveitis. Its role in the pathogenesis of silent chronic AU with and without arthritis needs further investigation.

摘要

目的

研究与幼年特发性关节炎(JIA)相关的葡萄膜炎患者房水中生物标志物的存在情况。

方法

使用表面增强激光解吸/电离飞行时间质谱(SELDI-TOF MS)分析了 116 名儿童的 73 份房水(AH)和 105 份血清样本。将样本分为 JIA 组、隐匿性慢性前葡萄膜炎(AU)组、其他葡萄膜炎实体组和非炎症对照组。使用 SELDI-TOF 生物标志物分析聚类向导进行统计生物标志物识别,然后进行多变量统计分析。通过聚丙烯酰胺凝胶蛋白分离和液相色谱串联质谱对生物标志物进行生化鉴定。在代表所有四个研究组的一些 AH 样本中进行 ELISA 检测。

结果

在 JIA 组中,与其他葡萄膜炎实体和对照组相比,质量电荷(m/z)13762 的一个 AH 蛋白峰在表达上存在定性和定量差异,但与隐匿性慢性 AU 组无差异。其在 JIA 和其他隐匿性慢性 AU 患者 AH 中的定量表达与葡萄膜炎活动呈正相关。在 AH 中 m/z 13762 的蛋白质被鉴定为转甲状腺素蛋白(TTR)。AH 中 TTR 浓度在研究组之间差异显著(P=0.006),m/z 13762 阳性的 JIA 和隐匿性慢性 AU 样本的 TTR 浓度明显高于其他葡萄膜炎和对照组。

结论

TTR 是 JIA 相关葡萄膜炎的潜在眼内生物标志物。其在有或无关节炎的隐匿性慢性 AU 发病机制中的作用需要进一步研究。

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