大疱性类天疱疮（BP）是一种常见的自身免疫性水疱病，致病性自身抗体与表皮基底膜带BP180等抗原结合并导致补体系统的激活是BP发病的关键环节。补体调节蛋白是一类具有调节补体活化作用的分子，其表达水平和功能异常与多种自身免疫性疾病密切相关。CD46是重要的补体调节蛋白之一，我们的研究发现，BP患者血清及疱液中sCD46明显高表达，并与补体C3a和BP180-NC16A致病性抗体滴度呈正相关，而皮损处mCD46表达水平明显低于正常人。在体外构建的BP病理模型中，降低mCD46的表达可使BP自身抗体介导的补体活化反应明显增强，提示mCD46和sCD46的表达失衡与BP发病密切相关。本课题拟在组织和细胞水平以及BP动物模型中验证CD46表达异常参与BP发病的具体环节和分子机制，从而阐明补体调控紊乱在BP发病中的地位和作用，为深入了解BP发病机制及治疗新策略提供新思路。

Bullous pemphigoid (BP) is an autoimmune bullous disease caused by autoantibodies against BP180 in the epidermal basement membrane. Autoantibody-mediated complement activation is an important process in BP pathogenesis. CD46, a crucial complement regulatory protein in the complement activation, has been reported to be involved in several autoimmune diseases. In the present study, we investigated whether CD46 plays a role in BP development. We found that sCD46 expression was significantly increased in the serum and blister fluids of BP patients and correlated with the levels of anti-BP180 NC16A antibody and C3a. Otherwise, the level of mCD46 was decreased in lesions of BP patients, whereas the complement activation was enhanced. We also found that mCD46 knockdown in HaCaT human keratinocytes enhanced autoantibody-mediated complement activation. These data suggest that mCD46 deficiency is an important factor in BP pathogenesis and the dysregulation of mCD46 and sCD46 is closely related to the pathogenesis of BP. Based on this, we are aimed to deepen our understanding on the pathogenesis of BP and to explore new specific therapeutic strategies by preventing complement activation via increasing CD46 levels.