Multiplex Autoantibody Profiling in SLE

SLE 中的多重自身抗体分析

• 批准号: 7235172
• 负责人: PAUL JOSEPH UTZ
• 金额: $ 4.19万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-01 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7235172
• 关键词: Multiplex; Autoantibody; Profiling; SLE

DESCRIPTION (provided by applicant): The broad, long-term objective of this proposal is to develop, validate, and employ protein and peptide autoantigen microarrays for profiling autoantibodies found in biological fluids. We will test the hypothesis that large-scale, parallel detection of autoantibody profiles can be used to explore epitope spreading, the role played by a subset of inflammatory cytokines in the initiation and propagation of autoimmunity, and ultimately in selection of antigen-specific tolerizing therapies. We have reduced to practice the use of large-scale arrays to identify autoantibody profiles in many human autoimmune diseases. We will use biochemical, immunological, and molecular biological techniques to validate and extend our ongoing protein array platform in exploring five specific aims in this proposal: (i.) to identify a universal surface chemistry for printing protein, peptide, and ribonucleoprotein complexes; (ii.) to validate autoantibody binding to individual features using highly-characterized serum samples and monoclonal antibodies; (iii.) to construct and validate a comprehensive CTD autoantigen array for detection of autoantibodies; (iv.) to use autoantigen microarrays to characterize serum and tissue-derived autoantibodies from spontaneous and inducible murine models of SLE; and (v.) to test the hypothesis that autoantibody profiling can be used as a surrogate marker of tolerance in animals treated with antigen-specific, DNA plasmid-based, tolerizing vaccines. The results of this proposal may elucidate an expanded role for B lymphocytes and their secreted products in autoimmunity, perhaps heralding an era of customized, antigen- or tissue- specific tolerizing therapy in humans. Moreover, further development of protein microarray technology will have broad applications to the fields of immunology, functional genomics, and proteomics.

描述（由申请人提供）：本提案的广泛、长期目标是开发、验证和采用蛋白质和肽自身抗原微阵列来分析生物体液中发现的自身抗体。我们将测试的假设，大规模，平行检测自身抗体谱可用于探索表位扩散，炎症细胞因子的子集在自身免疫的启动和传播中发挥的作用，并最终在选择抗原特异性耐受治疗。我们已经减少到实践中使用大规模阵列来识别许多人类自身免疫性疾病中的自身抗体谱。我们将使用生物化学，免疫学和分子生物学技术来验证和扩展我们正在进行的蛋白质阵列平台，以探索本提案中的五个具体目标：鉴定用于打印蛋白质、肽和核糖核蛋白复合物的通用表面化学;（ii.）使用高度表征的血清样本和单克隆抗体验证自身抗体与个体特征的结合;（iii.）构建并验证用于检测自身抗体的综合CTD自身抗原阵列;（iv.）使用自身抗原微阵列表征来自自发和诱导型SLE鼠模型的血清和组织来源的自身抗体;和（v.）以检验自身抗体谱可用作用抗原特异性、基于DNA质粒的耐受性疫苗治疗的动物中的耐受性的替代标记的假设。这一提议的结果可能阐明B淋巴细胞及其分泌产物在自身免疫中的扩大作用，可能预示着人类定制的抗原或组织特异性耐受治疗的时代的到来。此外，蛋白质微阵列技术的进一步发展将在免疫学、功能基因组学和蛋白质组学等领域有广泛的应用。