EPIDERMAL BULLOUS PEMPHIGOID ANTIGEN

表皮大疱性类天疱疮抗原

基本信息

批准号：
2748633
负责人：
NEIL J KORMAN
金额：
$ 11.49万
依托单位：
CASE WESTERN RESERVE UNIVERSITY
依托单位国家：
美国
项目类别：
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/2748633
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

项目摘要

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.

大胆的幽灵（BP）是人类皮肤的自身免疫性泡沫疾病其中循环的IgG自身抗体与大胆的Pemphigoid结合位于表皮基底膜的抗原（BPA）。 bp 自身抗体被认为在开始中起致病作用疾病，但是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卫星斑块。计划测试 BPA与其他人紧密相关的假设人类表皮中的半体斑点成分。我们将孤立使用各种洗涤剂从正常人皮肤中免疫沉淀BPA的BPA 提取条件并寻求230至180 kD之间的关联 BPA通过双重免疫沉淀测定法。我们将检查 Alpha6beta4整合素的关联，另一个Hemidesmosmal 成分和粘胶蛋白，最近描述组件，bpa by double（使用融合蛋白，源自BP cDNA克隆，与亲和力柱结合）和其他Hemidesmosmos 相关分子在内，包括静脉蛋白酶和A6b4整合素。另外，免疫电子显微镜将用于探测这些Hemidesmosamal成分之间的相互作用。我们还将寻求 BPA的基础区域与特定区域之间的关联角质形成细胞特异性角蛋白通过角蛋白融合蛋白结合到列。我们将确定BPA基因的基线定位在正常皮肤中。此外，我们将表征自动抗体 BP患者体内结合抗体的特异性进一步表征了BP中这两种抗体系统的重要性。皮肤，将使我们能够扩大对表皮地下室的了解膜结构。此外，这项研究可能会导致对 BP的发病机理，可以产生与更好患者有关的想法管理。该项目的长期目标是开发了解生物学对健康和疾病的生物学意义 BPA的。