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在人类自身免疫性葡萄膜炎的自发动物模型中,血清色素上皮衍生因子(PEDF)水平降低。

Serum PEDF levels are decreased in a spontaneous animal model for human autoimmune uveitis.

作者信息

Zipplies Johanna K, Hauck Stefanie M, Schoeffmann Stephanie, Amann Barbara, Stangassinger Manfred, Ueffing Marius, Deeg Cornelia A

机构信息

Institute of Animal Physiology, Department of Veterinary Sciences, LMU Munich, Veterinarstr. 13, D-80539 Munich, Germany.

出版信息

J Proteome Res. 2009 Feb;8(2):992-8. doi: 10.1021/pr800694y.

Abstract

Identification of biomarkers is of critical relevance toward improving diagnosis and therapy of autoimmune disorders. Serum markers are a desirable choice as sera are easily accessible and the development of assays for routine clinical detection prompts feasible. Autoimmune uveitis, a recurrent disease affecting the eye, is characterized by returning inflammatory attacks of the inner eye followed by variable periods of quiescent stages. Spontaneous equine recurrent uveitis (ERU) is the equine equivalent and serves as a model for the human disease. To identify potential biomarker candidates, we first systematically compared the proteomes of individual ERU cases with healthy controls by proteomic profiling using 2-D difference-gel-electrophoresis (2-D DIGE) followed by tandem mass spectrometry. A total of seven differentially expressed proteins were identified. Besides the upregulation of IgG and the significant lower expression of albumin, Antithrombin III, and Vitamin D binding protein, we found complement components C1q and C4, to be downregulated in uveitic state. Interestingly, Pigment epithelium-derived factor (PEDF), a marker already detected by 2DE differential proteome analysis in ERU target tissues, vitreous and retina, was found to be also significantly downregulated in sera. The lower expression of PEDF in sera of horses with uveitis could be verified in a cohort of 116 ERU cases and 115 healthy controls. Our findings of a significant lower PEDF expression in ERU cases also in the periphery of the eye proves PEDF as a promising uveitis biomarker.

摘要

生物标志物的鉴定对于改善自身免疫性疾病的诊断和治疗至关重要。血清标志物是一个理想的选择,因为血清易于获取,而且开发用于常规临床检测的检测方法切实可行。自身免疫性葡萄膜炎是一种影响眼睛的复发性疾病,其特征是眼内反复出现炎症发作,随后是不同时期的静止阶段。自发性马反复性葡萄膜炎(ERU)与之类似,可作为人类疾病的模型。为了确定潜在的生物标志物候选物,我们首先通过二维差异凝胶电泳(2-D DIGE)进行蛋白质组分析,随后进行串联质谱分析,系统地比较了个别ERU病例与健康对照的蛋白质组。共鉴定出7种差异表达的蛋白质。除了IgG上调以及抗凝血酶III和维生素D结合蛋白的表达显著降低外,我们还发现补体成分C1q和C4在葡萄膜炎状态下下调。有趣的是,色素上皮衍生因子(PEDF),一种已在ERU靶组织、玻璃体和视网膜的二维差异蛋白质组分析中检测到的标志物,在血清中也被发现显著下调。在116例ERU病例和115例健康对照的队列中,葡萄膜炎马匹血清中PEDF的低表达得到了验证。我们在眼周的ERU病例中也发现PEDF表达显著降低,这证明PEDF是一种有前景的葡萄膜炎生物标志物。

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