DERMATITIS HERPETIFORMIS & THE MUCOSAL IMMUNE RESPONSE

疱疹样皮炎（DH）是一种起泡性皮肤病， 特征性皮肤伊加沉积和相关的谷蛋白敏感性 肠病（GE）。 此外，当DH 患者坚持无麸质饮食。 这些发现表明 粘膜免疫应答可能在DH的发病机制中起重要作用。 本项目的目的是确定 的肠道和皮肤，并评估粘膜免疫反应， DH患者和正常人。 为了实现这一目标，我们将：1） 从DH患者的皮肤中提取伊加，确定洗脱的IgA的亚类。 伊加并评估其与正常人皮肤结合的能力，2）鉴定和 表征DH皮肤中结合伊加的抗原，并确定 抗原存在于正常人皮肤中，3）评估伊加从 血清、分泌物和分离的免疫复合物，以结合分离的 抗原，4）评估粘膜免疫应答，在血清和 分泌物，在DH患者以前遇到的饮食抗原 以及之前未遇到的抗原KLH。 角膜切片 将用缓冲液处理DH皮肤和正常人皮肤， 其能够从组织洗脱免疫复合物并溶解免疫复合物， 真皮表皮连接处 然后通过以下方法分析获得的洗脱液： 总伊加和伊加亚类的酶联免疫吸附测定（ELISA） 混合物. 还将使用SDS-PAGE分析洗脱液， 免疫印迹以检测伊加结合的抗原。 这些免疫印迹 将与来自血清、分泌物和分离的伊加反应 含有来自正常个体和DH的循环免疫复合物 患者 这些患者的粘膜免疫应答也将被 通过测量抗麦醇溶蛋白的血清和分泌抗体来评价， 和其它饮食抗原。 这些抗体将 以免疫球蛋白类和伊加亚类为特征。 的能力 患者对新抗原KLH的反应将通过喂养 患者和正常人KLH和评估血清和分泌 ELISA法检测抗体应答。 分泌与系统的关系 免疫力将通过尝试免疫这些相同的 肠免疫后皮下注射， 评估抗体反应。 这些研究将提供见解 深入了解DH的基本病理生理学，并增加我们对 肠形态异常（DH）患者的粘膜免疫应答 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.