Dermatology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Department of Physiopathology and Transplantation, Università degli Studi di Milano, Milan, Italy.
Front Immunol. 2019 Jul 2;10:1506. doi: 10.3389/fimmu.2019.01506. eCollection 2019.
There are several lines of evidence indicating that the physiopathological bases of bullous pemphigoid (BP), the most common subepidermal autoimmune bullous disease, are hallmarked by the production of autoantibodies directed against the hemidesmosomal anchoring proteins BP180 and BP230. In contrast to the robustness of the latter assumption, the multifaceted complexity of upstream and downstream mechanisms implied in the pathogenesis of BP remains an area of intense speculation. So far, an imbalance between T regulatory cells and autoreactive T helper (Th) cells has been regarded as the main pathogenic factor triggering the autoimmune response in BP patients. However, the contributory role of signaling pathways fostering the B cell stimulation, such as Toll-like receptor activation, as well as that of ancillary inflammatory mechanisms responsible for blister formation, such as Th17 axis stimulation and the activation of the coagulation cascade, are still a matter of debate. In the same way, the pathomechanisms implied in the loss of dermal-epidermal adhesion secondary to autoantibodies binding are not fully understood. Herein, we review in detail the current concepts and controversies on the complex pathogenesis of BP, shedding light on the most recent theories emerging from the literature.
有几条证据表明，大疱性类天疱疮（BP）的病理生理基础是以针对桥粒斑蛋白 BP180 和 BP230 的自身抗体产生为特征的，BP 是最常见的皮下自身免疫性大疱性疾病。与后一种假设的稳健性形成鲜明对比的是，BP 发病机制中涉及的上游和下游机制的多方面复杂性仍然是一个激烈推测的领域。到目前为止，T 调节细胞和自身反应性辅助性 T 细胞（Th）之间的失衡被认为是触发 BP 患者自身免疫反应的主要致病因素。然而，促进 B 细胞刺激的信号通路（如 Toll 样受体激活）以及负责水疱形成的辅助炎症机制（如 Th17 轴刺激和凝血级联激活）的贡献作用仍存在争议。同样，自身抗体结合导致真皮-表皮黏附丧失的病理机制尚不完全清楚。在此，我们详细回顾了 BP 复杂发病机制的当前概念和争议，阐明了文献中出现的最新理论。
