DERMATITIS HERPETIFORMIS AND THE MUCOSAL IMMUNE RESPONSE

描述：（逐字）疱疹样皮炎（DH）是一种起泡的皮肤 一种以皮肤伊加沉积物和 相关的，几乎总是无症状的，谷蛋白敏感性肠病（GSE）。的 粘膜免疫应答（MIR）在DH中的关键作用已被证实 通过观察发现，尽管GSE的临床症状缺乏， 大多数DH患者的皮肤表现可以得到控制 无麸质饮食允许发展的机制 皮肤伊加沉积和皮肤疾病，但防止发展， GSE的症状尚不清楚。这个项目的目的是描述 DH患者的MIR，以确定阻止 胃肠道疾病的临床体征的发展， 伊加的皮肤沉积和皮肤表现的发展 的DH。此外，该项目还将提供有关因素的新信息， 可能会改变和调节粘膜对饮食蛋白质的免疫反应， 以及粘膜炎症如何导致皮肤炎性疾病， 关节和其他器官。该项目的具体目标是：1。确定 具有DH和分离的GSE的抗原性患者和对照受试者使用 小肠T细胞的特异性和剂量反应的器官培养 分离的GSE的活检。2.循环中性粒细胞的表征 在小肠活检和麦胶蛋白肽患者中，其中一些诱导 疾病的DH对含麸质的饮食和水平的 细胞因子（IL-1/TNF α）/趋化因子（IL-8）在皮肤中的表达。皮肤活检 来自易发生皮肤损伤区域的DH患者（伸肌， 表面）和那些通常不发生皮肤损伤的区域（上 内臂）分析IL-1 α、TNF-α、IL-8和其它细胞/趋化因子 在控制皮肤病和无皮肤损伤期间的表达 在疾病活动期间。将在以下期间分析中性粒细胞： 存在和不存在皮肤损伤以评估激活水平， 在中性粒细胞迁移中起作用的细胞表面分子的表达 3.表达的T细胞Vb家族的CDR 3区的表征 DH患者和孤立性 症状性和无症状性GSE。来自患有结肠癌的患者的小肠的cDNA DH、孤立症状性GSE患者和孤立， 无症状（经治疗）GSE和非谷蛋白敏感性肠 将通过RT-PCR分析疾病的T细胞克隆性的证据 使用CDR 3谱型分析和单链构象分析， 多态性这些研究将有助于深入了解DH的发病机制 及单纯性GSE、MIR与皮肤的关系及影响因素 在控制人体粘膜免疫反应中很重要。

DESCRIPTION: (Verbatim) Dermatitis herpetiformis (DH) is a blistering skin disease characterized by the presence of cutaneous IgA deposits and an associated, almost always asymptomatic, gluten sensitive enteropathy (GSE). The critical role of the mucosal immune response (MIR) in DH has been demonstrated by the observation that, despite the lack of clinical symptoms of GSE in the majority of DH patients, the cutaneous manifestations of DH can be controlled by a gluten free diet. The mechanisms that allow for the development of cutaneous IgA deposits and skin disease yet that prevent the development of symptoms of GSE are not known. The purpose of this project is to characterize the MIR in patients with DH in order to determine the factors that prevent the development of clinical signs of gastrointestinal disease yet result in cutaneous deposits of IgA and the development of the cutaneous manifestations of DH. In addition, this project will provide new information regarding factors that may modify and regulate the mucosal immune response to dietary proteins in man and how mucosal inflammation results in inflammatory disease in the skin, joints and other organs. The specific aims of this project are: 1. Determine the antigenic patients with DH and isolated GSE and control subjects using organ culture of specificity and dose response of the T cells in small bowel biopsies from isolated GSE. 2. Characterization of the circulating neutrophils in patient with small bowel biopsies and gliadin peptides, some of which induce disease in DH on gluten containing diets and of the level of cytokine(IL-1/TNFa)/chemokine(IL-8) expression in the skin. Skin biopsies from patients with DH from areas predisposed to develop skin lesions (extensor, surfaces) and those areas which normally do not develop skin lesions (upper inner arm) will be analyzed for IL-1a, TNF-a, IL-8, and other cyto/chemokine expression during periods of control of the skin disease and no skin lesions and during disease activity. Neutrophils will be analyzed during periods when skin lesions are present and not present to assess the level of activation and expression of cell surface molecules which play a role in neutrophil migration 3. Characterization of the CDR3 region of the T cell Vb families expressed in the small bowel biopsies of patients with DH and of patients with isolated symptomatic and asymptomatic GSE. cDNA from the small bowel of patients with DH, patients with isolated symptomatic GSE and patients with isolated, asymptomatic (treated) GSE and patients with non-gluten sensitive intestinal disease will be analyzed by RT-PCR for the evidence of clonality of the T cells in the gut using CDR3 spectrotype analysis and single strand conformational polymorphisms. These studies will provide insights into the pathogenesis of DH and isolated GSE, the relationship between the MIR and the skin and factors important in controlling the mucosal immune response in man.