EPIDERMAL BULLOUS PEMPHIGOID ANTIGEN

表皮大疱性类天疱疮抗原

• 批准号: 2080404
• 负责人: NEIL J KORMAN
• 金额: $ 9.96万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-08-01 至 1999-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2080404
• 关键词: antigen antibody reaction; autoantigens; autoimmune disorder; basement membrane; human subject; immunoelectron microscopy; immunoglobulin G; immunoprecipitation; integrins; intercellular connection; keratin; keratinocyte; keratosis; protein purification; skin; vesicular skin disorder

Bullous pemphigoid (BP) is an autoimmune blistering disease of human skin in which circulating IgG autoantibodies bind to bullous pemphigoid antigens (BPA's) located in the epidermal basement membrane. BP autoantibodies are thought to play a pathogenic role in the initiation of disease, however the factor which stimulate autoantibody production are unknown. Ultrastructural studies reveal that BPA's localize to the hemidesmosomal plaque of basal epidermal cells. It is planned to test the hypothesis that BPA's are tightly associated with other hemidesmosomal components in human epidermis. We will isolated and immunoprecipitate BPA's from normal human skin using various detergent extraction conditions and seek associations between the 230 and 180 KD BPA's by means of double immunoprecipitation assays. We will examine the association of the alpha6Beta4 integrin, another hemidesmosomal component, and epiligrin, a recently described hemidesmosomal associated component, with BPA's by double (using fusion proteins, derived from BP cDNA clones, bound to affinity columns) and other hemidesmosome associated molecules including epiligrin and the a6B4 integrin. Additionally, immunoelectron microscopy will be used to probe for interactions among these hemidesmosomal components. We will also seek association between BPA's and particular regions of the basal keratinocyte specific keratins by means of keratins fusion proteins bound to columns. We will determine the baseline localization of the BPA genes in normal skin. In addition, we will characterize the autoantibody specificity of the in vivo bound antibodies in patients with BP to further characterize the importance of these two antibody systems in BP. skin and will allow us to expand our knowledge of epidermal basement membrane structure. Furthermore, this research may lead to insights into the pathogenesis of BP which could yield ideas relevant to better patient management. The long term objective of this project is to develop an understanding of the biological significance in health and disease of the BPA's.

大疱性类天疱疮（BP）是一种人类皮肤自身免疫性水疱病 其中循环 IgG 自身抗体与大疱性类天疱疮结合 抗原（BPA）位于表皮基底膜。 血压 自身抗体被认为在起始过程中发挥致病作用 疾病，然而刺激自身抗体产生的因素 未知。超微结构研究表明 BPA 位于 基底表皮细胞的半桥粒斑。 计划测试 BPA 与其他物质密切相关的假设 人表皮中的半桥粒成分。 我们将隔离并 使用各种清洁剂从正常人体皮肤中免疫沉淀 BPA 提取条件并寻求 230 和 180 KD 之间的关联 通过双重免疫沉淀分析检测 BPA。 我们将检查 α6Beta4 整合素（另一种半桥粒）的关联 成分，以及 Epiligrin，一种最近描述的半桥粒相关的 成分，双 BPA（使用源自 BP 的融合蛋白 cDNA 克隆，结合到亲和柱）和其他半桥粒 相关分子包括 epiligrin 和 a6B4 整合素。 此外，免疫电子显微镜将用于探测 这些半桥粒成分之间的相互作用。 我们也将寻求 BPA 与基底层特定区域之间的关联 通过角蛋白融合蛋白结合的角质形成细胞特异性角蛋白 到列。 我们将确定 BPA 基因的基线定位 在正常皮肤中。 此外，我们还将表征自身抗体 BP 患者体内结合抗体的特异性 进一步表征了这两种抗体系统在BP中的重要性。 皮肤，将使我们能够扩展我们对表皮基底的了解 膜结构。 此外，这项研究可能会带来以下见解： BP 的发病机制可能会产生与更好的患者相关的想法 管理。 该项目的长期目标是开发一个 了解生物体对健康和疾病的生物学意义 BPA 的。