DERMATITIS HERPETIFORMIS & THE MUCOSAL IMMUNE RESPONSE

疱疹样皮炎是一种水疱性皮肤病。 以皮肤上存在的IgA沉积为特征的， 相关的面筋过敏性肠病，以及高发的 HLAB8/DR3单倍型。这个项目的目的是 研究粘膜免疫反应(MIR)的作用 皮肤免疫球蛋白A沉积与人类白细胞抗原相关性 精神分裂症的病理生理学。具体目标是：1.确定 血清抗体与分泌型抗体的关系 抗饮食抗原及其来源的重要因素 和抗原特异性。2.肝豆状核变性患者血清中IgA的洗脱及特征 皮肤。3.确定皮肤组织中的IgA结合部位。4. 研究人类白细胞抗原II类区域基因结构的性质 确定DH患者是否存在独特的差异。 猪传染性支气管炎血清抗体与分泌型抗体的关系 饮食抗原将通过比较等电点来确定。 聚焦(IEF)谱型和独特型(ID)分析 专一性。抗膳食抗体亲和纯化的IgA抗体 抗原将被用来提高抗ID抗体。这些抗ID 抗体将被用来确定交叉反应独特型 (CRI)存在于DH患者的分泌物和血清中 抗体表达CRI，如果皮肤IgA沉积表达 CRI。抗膳食抗原的血清和分泌型IgA抗体 将被检查与其他饮食的交叉反应 人腺病毒的抗原性和抗原性。免疫球蛋白结合 将使用金标记物确定DH皮肤中的结构 抗体和免疫电子显微镜。此外, 水解酶与正常成纤维细胞的免疫沉淀实验 将对真皮微纤维的性质进行评估 蛋白质和IgA结合蛋白。免疫球蛋白从水解液中洗脱出来 从血清中提纯的亲和力将用IEF进行分析和测试 适用于正常皮肤和水痘皮肤。最后，基因组DNA来自 健康受试者和健康受试者将被检查使用 检测人类白细胞抗原DP、DQ和DR基因的表达 区域基因表现出独特的多态现象。这些研究将 提供了对DH的病理生理学及其相互关系的见解 粘膜抗原的血清和分泌型IgA反应的研究 暴露和人类白细胞抗原关联在自身免疫性疾病中的作用。

Dermatitis herpetiformis (DH) is a blistering skin disease characterized by the presence of cutaneous deposits of IgA, an associated gluten sensitive enteropathy, and a high incidence of the HLA B8/DR3 haplotype. The purpose of this project is to investigate the role of the mucosal immune response (MIR), the cutaneous IgA deposits and the HLA association in the pathophysiology of DH. The specific aims are: 1. Determine the relationship between serum and secretory antibodies directed against dietary antigens and the factors important in their origin and antigenic specificity. 2. Elute and characterize the IgA in DH skin. 3. Characterize the IgA binding sites in DH skin. 4. Investigate the nature of the HLA class II region gene structure to determine if unique differences are present in patients with DH. The relationship between serum and secretory antibodies to dietary antigens will be determined by comparing isoelectric focusing (IEF) spectrotypes and analysis of idiotypic (Id) specificity. Affinity purified IgA antibodies against dietary antigens will be used to raise anti-Id antibodies. These anti-Id antibodies will be used to determine if cross-reactive idiotypes (CRI) are present in patients with DH, if secretory and serum antibodies express CRI and if the cutaneous IgA deposits express CRI. Serum and secretory IgA antibodies against dietary antigens will be examined for cross-reactivity against other dietary antigens and against peptides from human adenovirus. IgA binding structures in DH skin will be determined using gold labeled antibodies and immunoelectron microscopy. In addition, immunoprecipitation experiments using DH and normal fibroblasts will be done to evaluate the nature of dermal micro-fibrillar proteins and IgA binding proteins. IgA eluted from DH skin and affinity purified from serum will be analyzed by IEF and tested for binding to normal and DH skin. Finally, genomic DNA from patients with DH and normal subjects will be examined using cDNA for HLA DP, DQ and DR genes to determine if HLA class II region gene express distinctive polymorphisms. These studies will provide insights into the pathophysiology of DH, the relationship of the serum and secretory IgA responses to mucosal antigen exposure and the role of HLA associations in autoimmune disease.