DERMATITIS HERPETIFORMIS & THE MUCOSAL IMMUNE RESPONSE

疱疹样皮炎是一种水疱性皮肤病。 特异性的IgA皮肤沉积和相关的面筋敏感 肠病(GE)。此外，注意到临床改善时，卫生署 患者坚持无麸质饮食。这些发现表明， 粘膜免疫反应可能在DH的发病机制中起中心作用。 这个项目的目的将是确定 对肠道和皮肤的影响，并评价其粘膜免疫反应。 卫生署病人及正常人。要做到这一点，我们将：洗脱 从DH患者皮肤中提取免疫球蛋白，确定被洗脱者的亚类 免疫球蛋白和评估其与正常人皮肤结合的能力，2)识别和 鉴定与IgA结合的皮肤中的抗原，并确定 抗原存在于正常人皮肤中，3)评估IgA从 血清、分泌物和分离的免疫复合体与分离的 抗原，4)评估粘膜免疫反应，在血清和 卫生署患者的分泌物与既往饮食抗原有关 以及一种以前从未遇到过的抗原K1H。角膜刀切面 的皮肤和正常人皮肤将用缓冲液处理，这些缓冲液是 能够从组织中洗脱免疫复合体并溶解 真皮-表皮交界处。所获得的洗脱液将被分析 酶联免疫吸附测定法测定总IgA及其亚类 组成。洗脱液也将用十二烷基硫酸钠-聚丙烯酰胺凝胶电泳法和 免疫印迹法检测IgA结合的抗原。这些免疫印迹 将与血清、分泌物和分离的IgA中的IgA反应 含有正常人和猪瘟患者的循环免疫复合体 病人。这些患者的粘膜免疫反应也将是 通过检测血清和分泌的抗醇溶蛋白抗体进行评估， 和其他饮食抗原使用酶联免疫吸附试验。这些抗体将是 具有免疫球蛋白类和免疫球蛋白A亚类的特征。的能力 患者对一种新的抗原KLH的反应将通过喂食来确定 患者和正常人KLH值及血清和分泌物的测定 酶联免疫吸附试验检测抗体。分泌性与系统性的关系 免疫力将通过尝试免疫这些人来进行调查 肠内免疫后皮下注射的个体和 对抗体反应的评估。这些研究将提供真知灼见 深入了解卫生署的基本病理生理学，并加深我们对 肠道形态异常患者的黏膜免疫反应 GSE)和正常个体。

Dermatitis herpetiformis (DH) is a blistering skin disease with characteristic cutaneous deposits of IgA and an associated gluten sensitive enteropathy (GE). In addition, clinical improvement is noted when DH patients adhere to a gluten-free diet. These findings suggest that the mucosal immune response may play a central role in the pathogenesis of DH. The purpose of this project will be to determine the relationship between the gut and the skin in DH and to evaluate the mucosal immune response of DH patient and normal individuals. To accomplish this we will: 1) elute IgA from the skin of patients with DH, determine the subclass of the eluted IgA and assess its ability to bind to normal human skin, 2) identify and characterize the antigen in DH skin which binds IgA and determine if that antigen is present in normal human skin, 3) assess the ability of IgA from serum, secretions, and isolated immune complexes to bind to the isolated antigen, 4) evaluate the mucosal immune response, in both serum and secretions, in patients with DH to previously encountered dietary antigens as well as to a previously unencountered antigen, KLH. Keratome sections of DH skin and normal human skin will be treated with buffers which are capable of eluting immune complexes from tissue and of solubilizing the dermal-epidermal junction. The eluates obtained will then be analyzed by enzyme linked immunoadsorbent assay (ELISA) for total IgA and IgA subclass composition. The eluates will also be analyzed using SDS-PAGE and immunoblot to detect the antigen to which IgA binds. These immunoblots will be reacted with IgA from serum, secretions, and isolated IgA containing circulating immune complexes from both normal individuals and DH patients. The mucosal immune response of these patients will also be evaluated by measuring both serum and secretory antibodies against gliadin, and other dietary antigens using ELISA. These antibodies will be characterized as to immunoglobulin class and IgA subclass. The ability of patients to respond to a new antigen, KLH, will be determined by feeding patients and normal individuals KLH and assessing the serum and secretory antibody respsne by ELISA. The relationship between secretory and systemic immunity will be investigated by attempting to immunize these same indivduals by subcutaneous injection after enteric immunization and assessment of the antibody response. These studies will provide insights into the basic pathophysiology of DH, and increase our understanding of the mucosal immune response in patients with abnormal intestinal morphology (DH with GSE) and in normal individuals.