EPIDERMAL BULLOUS PEMPHIGOID ANTIGEN

大疱性类天疱疮是一种自身免疫性皮肤水疱病 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。 BP 自身抗体被认为在启动中起致病作用， 然而，刺激自身抗体产生的因素 是未知的。超微结构研究表明，BPA的本地化， 基底表皮细胞的半桥粒斑。 计划测试 假设BPA与其他 人表皮中的半桥粒成分。 我们将被孤立， 使用各种去污剂从正常人皮肤免疫沉淀BPA 提取条件，并寻求230和180 KD之间的关联 BPA的双免疫沉淀试验。 我们会研究 α 6 β 4整联蛋白，另一种半桥粒 成分，和epiligrin，最近描述的半桥粒相关 组分，与BPA的两倍（使用融合蛋白，来自BP cDNA克隆，与亲和柱结合）和其他半桥粒 相关分子包括epiligrin和α 6 β 4整联蛋白。 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。 我们还将寻求 BPA与基底细胞特定区域之间的联系 通过角蛋白融合蛋白结合的角质细胞特异性角蛋白 到列。 我们将确定BPA基因的基线定位 在正常的皮肤。 此外，我们将描述自身抗体 BP患者体内结合抗体对 进一步表征这两种抗体系统在BP中的重要性。 皮肤，并将使我们扩大我们的知识，表皮基底 膜结构 此外，这项研究可能会导致洞察 BP的发病机制，这可能会产生相关的想法，更好的病人 管理 该项目的长期目标是开发一个 了解人类的健康和疾病在生物学上的重要性 BPA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.