DERMATITIS HERPETIFORMIS & THE MUCOSAL IMMUNE RESPONSE

疱疹样皮炎（DH）是一种起泡性皮肤病 其特征在于存在伊加的皮肤沉积物， 与麸质敏感性肠病相关， HLA B8/DR 3单倍型。 该项目的目的是 研究粘膜免疫反应（MIR）的作用， 皮肤伊加沉积和HLA相关性 DH的病理生理学 具体目标是：1. 确定 血清和分泌性抗体之间的关系 针对饮食抗原和其来源的重要因素 和抗原特异性。 2.洗脱并表征DH中的伊加 皮肤 3.表征DH皮肤中的伊加结合位点。 4. 研究HLA II类区域基因结构的性质， 确定DH患者中是否存在独特的差异。 血清和分泌性抗-HBs的关系 饮食抗原将通过比较等电 聚焦（IEF）谱型和独特型（Id）分析 的特异性 亲和纯化的伊加抗体 抗原将用于产生抗Id抗体。 这些反身份证 抗体将用于确定是否交叉反应独特型 (CRI)存在于DH患者中，如果分泌和血清 抗体表达CRI，如果皮肤伊加沉积物表达CRI， CRI. 抗食物抗原的血清和分泌伊加抗体 将检查与其他饮食的交叉反应性 抗原和抗来自人腺病毒的肽。 伊加结合 DH皮肤中的结构将使用金标记的 抗体和免疫电镜。 此外，本发明还提供了一种方法， 使用DH和正常成纤维细胞的免疫沉淀实验 将进行评价真皮微纤维的性质， 蛋白和伊加结合蛋白。 从DH皮肤洗脱的伊加， 将通过IEF分析从血清中纯化的亲和力，并检测 用于与正常和DH皮肤结合。 最后，来自 DH患者和正常受试者将使用 HLA DP、DQ和DR基因的cDNA，以确定HLA II类 区域基因表现出独特的多态性。 这些研究将 提供深入了解DH的病理生理学， 对粘膜抗原的血清和分泌型伊加应答 暴露和HLA相关性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.