Lübeck Institute of Experimental Dermatology and Department of Dermatology, University of Lübeck, Lübeck, Germany.
Exp Dermatol. 2017 Dec;26(12):1179-1186. doi: 10.1111/exd.13335. Epub 2017 May 9.
Pemphigoid diseases (PDs) are chronic and life-threatening autoimmune diseases of the skin and mucous membranes. PDs are characterized and caused by autoantibodies targeting components of the basement membrane. In the PD epidermolysis bullosa acquisita (EBA), the target autoantigen is type VII collagen. Current treatment options of PD, especially EBA, are limited and are mostly based on systemic immunosuppression. Animal models of PD have greatly advanced our understanding of PD pathogenesis. This has led to the identification of several novel therapeutic targets, including signalling molecules. Herein, the contribution of signalling molecules in the pathogenesis of the PD EBA and the effects of pharmacological targeting of these pathways are reviewed in detail. The p38 MAPK, ERK1/2, AKT, PI3Kβ, Hsp90, RORα, PDE4, Src kinases and CARD9 have been demonstrated to be critically involved in EBA pathogenesis. With the advent of new signal transduction inhibitors, we expect that the so far poor prognosis of EBA and other PD will improve significantly in the future.
天疱疮病（PDs）是一种慢性且危及生命的皮肤和黏膜自身免疫性疾病。PDs 的特征和病因是针对基底膜成分的自身抗体。在 PD 中的大疱性类天疱疮（EBA）中，靶自身抗原是 VII 型胶原。目前 PD 的治疗选择，特别是 EBA，是有限的，并且大多基于全身免疫抑制。PD 的动物模型极大地促进了我们对 PD 发病机制的理解。这导致了几个新的治疗靶点的确定，包括信号分子。本文详细综述了信号分子在 PD EBA 发病机制中的作用以及针对这些途径的药理学靶向作用。p38 MAPK、ERK1/2、AKT、PI3Kβ、Hsp90、RORα、PDE4、Src 激酶和 CARD9 已被证明在 EBA 发病机制中起关键作用。随着新的信号转导抑制剂的出现，我们预计 EBA 和其他 PD 的预后将在未来得到显著改善。
