SEROLOGICAL EXPRESSION ANALYSIS OF VITILIGO AND ALOPECIA

描述（取自应用程序）： 对皮肤及其附件成分的自身免疫反应产生一种 皮肤病的范围。白癜风，以部分或完全丧失为特征 皮肤色素沉着和斑秃， 有两种这样的疾病。有趣的是，虽然某些自身免疫性皮肤病 例如由限于特定成分反应引起的大疱性疾病 白癜风和脱发往往表现为与其他 自身免疫性疾病这表明对自身抗原的免疫耐受性 产生黑色素的细胞和毛囊中的细胞被破坏 相对容易。这些抗原的分子特性和免疫调节剂的作用 体液免疫应答与细胞免疫应答在这些疾病发病机制中的作用 仍然未知。采用生物化学和免疫细胞化学技术， 鉴定患者血清中自身抗体识别的抗原， 未能产生这些疾病中靶抗原的确定性知识。 同样，在分析和描述T 淋巴细胞在体外的作用已经排除了广泛的研究，T细胞在 白癜风和脱发的发病机制。领域的最新发展 人类肿瘤免疫学提供了克服这些局限性机会， 自身免疫性皮肤中免疫应答靶的分子鉴定 紊乱首先，已经证明筛选cDNA表达， 具有来自癌症患者的血清抗体的文库可用于鉴定 体液应答的抗原靶点。第二，这种筛选方法，称为 SEREX还允许鉴定细胞毒性CD8 T细胞识别的抗原 癌症患者体内的细胞。再加上最近的研究表明， HLA II类限制性CD4 T细胞对肿瘤抗原的识别 CD8细胞，SEREX分析的这些观察结果强化了 自身抗原同时呈递给体液和细胞免疫 系统.这就提出了用血清进行SEREX分析的可能性， 自身免疫性皮肤病患者可以识别 由抗体和T细胞识别的组织特异性抗原。分子 鉴定这些细胞中免疫反应的靶向抗原阵列 疾病将有助于阐明其发病机制。我们建议 从新生黑素细胞的混合培养物产生cDNA表达文库 从不同种族背景和混合毛囊中获得 从正常头皮活检中显微解剖出来的。这些表达式库将 为开始提供无限量的组织特异性基因产物的来源 通过SEREX分析剖析免疫应答。预计这样 分析将允许鉴定抗体和T细胞的靶 白癜风和斑秃的治疗反应。

DESCRIPTION (Taken from the application): Autoimmune reactions to components of skin and its appendages produce a spectrum of skin diseases. Vitiligo, characterized by partial or complete loss of skin pigmentation and alopecia areata, a chronic inflammatory hair disorder are two such diseases. Interestingly, while certain autoimmune skin disorders such as bullous diseases result from reactions limited to specific components of skin, vitiligo and alopecia often manifest in association with other autoimmune diseases. This suggests that immune tolerance to self-antigens on pigment producing melanocytes and cells in the hair follicles is broken relatively easily. The molecular identity of these antigens and the role of humoral vs. cellular immune responses in the pathogenesis of these diseases remain unknown. Biochemical and immunocytochemical techniques employed to identify antigens recognized by autoantibodies in the sera of patients have failed to yield definitive knowledge of target antigens in these disorders. Similarly, methodological limitations in analyzing and characterizing T lymphocytes in vitro have precluded extensive studies on the role of T cells in the pathogenesis of vitiligo and alopecia. Recent developments in the field of human tumor immunology provide an opportunity to overcome these limitations on molecular identification of targets for immune responses in autoimmune skin disorders. First, it has been demonstrated that screening cDNA expression libraries with serum antibodies from cancer patients can be used to identify antigen targets for humoral responses. Second, this screening method, termed SEREX, also allows identification of antigens recognized by cytotoxic CD8 T cells in patients with cancer. Together with recent studies that showed the presence of HLA class II-restricted CD4 T cells to tumor antigen recognized by CD8 cells, these observations from SEREX analysis reinforce the concept of simultaneous presentation of self-antigens to humoral and cellular immune systems. This raises the possibility that SEREX analysis with sera from patients with autoimmune skin disorders could allow identification of tissue-specific antigens recognized by antibodies and T cells. Molecular identification of the array of antigens targeted for immune response in these diseases will help delineate mechanisms of their pathogenesis. We propose to generate cDNA expression libraries from pooled cultures of neonatal melanocytes obtained from different racial backgrounds and pooled hair follicles microdissected from normal scalp biopsies. These expression libraries will provide a source of unlimited supply of tissue-specific gene products to begin dissecting immune responses by SEREX analysis. It is expected that such analysis will allow identification of targets for both antibody and T cell responses in vitiligo and alopecia areata.