Evolution of the pathogenic autoimmun response in bullous pemphigoid

大疱性类天疱疮致病性自身免疫反应的演变

基本信息

批准号：
202300395
负责人：
Professor Dr. Michael Hertl
金额：
--
依托单位：
Klinik für Dermatologie und Venerologie
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2012
资助国家：
德国
起止时间：
2011-12-31 至 2018-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/202300395?language=en
关键词：
Evolution pathogenic autoimmun response bullous

项目摘要

Autoimmune diseases, similarly to cancer, generally show an increased frequency at higher age. While mechanisms of autoaggressive tissue damage have been increasingly investigated, the progression from autoimmunity to a pathogenic autoantibody response resulting in clinically overt disease is largely unexplored. The pemphigoids comprise a group of immunobullous skin disorders which affect the elderly and are typically preceded by a prodromal non-bullous stage. Therefore, the pemphigoids represent an exquisite model to study the initiation and regulation of a pathogenic autoimmune response in ageing individuals. By connecting basic to clinical research, the present project will allow to characterize the pathogenic mechanisms of the initiation of autoimmunity and its coupling to tissue damage in pemphigoids. Specifically, the autoantigenic epitopes that are recognized by autoreactive T cells as well as different possible determinants of the autoantibody pathogenicity, including their molecular specificity, isotype and glycosylation will be characterized in patients with “pre-pemphigoid” and full-blown pemphigoid as well as in a recently established mouse model of pemphigoid. In addition, to new mechanistic insights, the results of the present study will greatly facilitate the identification of subjects at risk to develop pemphigoid, the development of new diagnostic and prognostic tools, and of more effective therapeutic strategies. Importantly, new insights into the pathogenesis of the pemphigoids and newly developed diagnostic tools may be translated to more comprehensive research and, eventually, the management of other age-related inflammatory and autoimmune disorders.

与癌症类似的自身免疫性疾病通常显示出更高年龄的频率增加。虽然已经增加了自身攻击组织损伤的机制，但从自身免疫到致病性自身抗体反应，导致临床明显的疾病的发展是意外的。雌雄同体包括一组影响老年人的免疫性皮肤疾病，通常是前驱阶段。因此，雌雄同体代表了研究衰老个体中致病性自身免疫反应的主动性和调节的独家模型。通过将基本研究与临床研究联系起来，本项目将允许表征自身免疫性倡议的致病机制及其与Pemphigoids中组织损伤的耦合。具体而言，由自身反应性T细胞识别的自身抗原表位以及自身抗体致病性的不同可能的决定剂，包括其分子特异性，同型和糖基化的特征在于具有“ prespemphigoid”的患者和最近建立的Pemphigoid and e pemphigigip spemphigigipigip sepemigipigip and pemphigip spemoidepigigip and pemphigigip s pemphigigipigigip emphigip emphigip and pemphigigibigip emphigip and pemphigib sepphigibigip。此外，对于新的机械见解，本研究的结果将在很大程度上支持鉴定有风险发展的受试者，开发新的诊断和预后工具以及更有效的治疗策略。重要的是，可以将新见解的新见解和新开发的诊断工具转化为更全面的研究，并最终管理其他与年龄相关的炎症性和自身免疫性疾病。