EPIDERMAL BULLOUS PEMPHIGOID ANTIGEN

大疱性类天疱疮(BP)是一种人类皮肤的自身免疫性水疱病。 循环中的免疫球蛋白抗体与大疱性类天疱疮结合 抗原(BPA‘s)位于表皮基底膜。BP 自身抗体被认为在发病过程中起着致病作用。 然而，刺激自身抗体产生的因素 都是未知的。超微结构研究表明，BPA定位于 基生表皮细胞的半嵌合体斑块。它计划测试 双酚A与其他物质密切相关的假设 人表皮中的半桥体成分。我们将孤立和 用多种洗涤剂免疫沉淀正常人皮肤中的双酚A 提取条件和寻找230 kD和180 kD之间的关联 双抗体夹心免疫沉淀法。我们将研究 另一种半染色体与α6β4整合素的相关性 组分，以及最近描述的与半桥粒相关的外植素 成分，与双酚A的加倍(使用融合蛋白，源自BP 与亲和柱结合的cDNA克隆)和其他半桥粒 相关分子包括外膜蛋白和a6B4整合素。 此外，免疫电子显微镜将用于探测 这些半染色体组分之间的相互作用。我们还将寻求 双酚A与基底的特定区域之间的关系 结合角蛋白融合蛋白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。 穿着正常皮肤。此外，我们还将对自身抗体进行表征 BP患者体内结合抗体的特异性 进一步说明这两种抗体系统在BP中的重要性。 皮肤，并将使我们扩大我们对表皮基底的知识 膜结构。此外，这项研究可能会导致对 BP的发病机制可以为更好的患者提供相关的想法 管理层。这个项目的长期目标是开发一种 对人的健康和疾病的生物学意义的理解 双酚A的。

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.