Department of Dermatology, Allergy, and Venerology, University of Lübeck, Lübeck, Germany.
Lübeck Institute of Experimental Dermatology (LIED), University of Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany.
Semin Immunopathol. 2019 Nov;41(6):645-654. doi: 10.1007/s00281-019-00759-y. Epub 2019 Nov 15.
Pemphigoid diseases are a group of autoimmune blistering skin diseases defined by an immune response against certain components of the dermal-epidermal adhesion complex. They are prototypical, autoantibody-driven, organ-specific diseases with the emergence of inflammatory skin lesions dependent on the recruitment of immune cells, particularly granulocytes, into the skin. During an acute flare of disease, inflammatory skin lesions typically progressing from erythema through urticarial plaques to subepidermal blisters erosions erupt and, finally, completely resolve, thus illustrating that resolution of inflammation is continuously executed in pemphigoid disease patients and can be directly monitored on the skin. Despite these superb conditions for examining resolution in pemphigoid diseases as paradigm diseases for antibody-induced tissue inflammation, the mechanisms of resolution in pemphigoid are underinvestigated and still largely elusive. In the last decade, mouse models for pemphigoid diseases were developed, which have been instrumental to identify several key pathways for the initiation of inflammation in these diseases. More recently, also protective pathways, specifically IL-10 and C5aR2 signalling on the molecular level and T on the cellular level, counteracting skin inflammation have been highlighted and may contribute to the continuous execution of resolution in pemphigoid diseases. The upstream orchestrators of this process are currently under investigation. Pemphigoid disease patients, particularly bullous pemphigoid patients, who are predominantly above 75 years of age, often succumb to the side effects of the immunosuppressive therapeutics nowadays still required to suppress the disease. Pemphigoid disease patients may therefore represent a group of patients benefiting most substantially from the introduction of non-immunosuppressive, proresolving therapeutics into the treatment regimens for their disease.
天疱疮病是一组自身免疫性水疱性皮肤病，其特征是针对皮肤-表皮黏附复合体的某些成分发生免疫反应。它们是典型的、自身抗体驱动的、器官特异性疾病，炎症性皮肤损伤的出现依赖于免疫细胞，特别是粒细胞，向皮肤的募集。在疾病的急性发作期间，炎症性皮肤损伤通常从红斑通过荨麻疹样斑块发展到表皮下水疱、糜烂，最终完全消退，因此表明天疱疮病患者的炎症消退是持续进行的，可以直接在皮肤上监测。尽管天疱疮病作为抗体诱导的组织炎症的范例疾病具有如此优越的检查消退的条件，但天疱疮病的消退机制仍未得到充分研究，仍然很大程度上难以捉摸。在过去的十年中，开发了天疱疮病的小鼠模型，这些模型对于确定这些疾病中炎症起始的几个关键途径至关重要。最近，也强调了针对炎症的保护性途径，特别是在分子水平上的 IL-10 和 C5aR2 信号以及细胞水平上的 T 细胞，这些途径可以对抗皮肤炎症，并可能有助于天疱疮病的持续消退。目前正在研究该过程的上游协调器。天疱疮病患者，特别是大疱性类天疱疮患者，他们主要年龄在 75 岁以上，经常因目前仍需要抑制疾病的免疫抑制治疗的副作用而屈服。因此，天疱疮病患者可能是受益于将非免疫抑制性、促消退治疗引入其疾病治疗方案的最大的患者群体之一。
