白塞病新特异性自身抗体筛选及靶抗原与发病机制研究

Behcet's disease (BD) is a common autoimmune disease with unknown etiology, high incidence and multiple organ dysfunction. Due to lack of sensitive and specific laboratory indexes, BD is diagnosed based on clinical manifestations. Previously, we employed the human proteome (HuProt) arrays and identified a BD-specific autoantibody, anti-CTDP1 autoantibody. However, anti-CTDP1 autoantibody only has a sensitivity of 23.86%, which limits its clinical application. In this project, we will employ Nucleic Acid Programmable Protein Arrays (NAPPA) to identify novel BD-specific biomarkers using a Three-Phase strategy. The successful implementation of this project will discover novel BD-specific autoantibodies which are helpful in the early diagnosis, the differential diagnosis and the evaluation of disease activity of BD. In addition, the epitopes, the structures, the properties and the interaction proteins of autoantigen will be examined using mass-spectrometric techniques, proteomics and bioinformatics techniques, and the association between autoantigen and pathogenesis of BD will be studied as well.

白塞病（BD）是病因不明、高发病率、多器官损伤的常见自身免疫性疾病，目前临床诊断主要基于临床表现，缺乏敏感、特异的实验室检查指标。前期基于人类全基因组编码蛋白高密度纯化蛋白质芯片，发现BD特异性自身抗体抗CTDP1抗体，但敏感性仅有23.86%，临床应用存在局限性。本研究基于核酸可编程蛋白质芯片技术（Nucleic Acid Programmable Protein Arrays，NAPPA) 平台，采用筛选-验证-确认的可靠研究方案，期望发现与BD早期诊断、鉴别诊断和病情评估相关的特异性新型自身抗体标记物分子，采用质谱、蛋白质组学及生物信息学技术，研究特异性靶抗原的抗原表位、蛋白结构、蛋白特性及互相作用蛋白质，探讨靶抗原引起机体免疫反应的性质以及与BD发病机制之间的关系。

白塞病（BD）是病因不明、高发病率、多器官损伤的常见自身免疫性疾病，目前临床诊断主要基于临床表现，缺乏敏感、特异的实验室检查指标。前期基于人类全基因组编码蛋白高密度纯化蛋白质芯片，发现BD特异性自身抗体抗CTDP1抗体，但敏感性仅有23.86%，临床应用存在局限性。本研究基于核酸可编程蛋白质芯片技术（Nucleic Acid Programmable Protein Arrays，NAPPA) 平台，以及自主研发的人类蛋白芯片V1.0，该芯片含有2800个纯化蛋白及1500个翻译后修饰抗原，采用筛选-验证-确认的可靠研究方案，期望发现与BD早期诊断、鉴别诊断和病情评估相关的特异性新型自身抗体标记物分子，采用质谱、蛋白质组学及生物信息学技术，研究特异性靶抗原的抗原表位、蛋白结构、蛋白特性及互相作用蛋白质，探讨靶抗原引起机体免疫反应的性质以及与BD发病机制之间的关系。

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