PEDEGO Research Unit, Oulu Center for Cell-Matrix Research, Department of Dermatology and Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.
Institute for Medical Microbiology and Hygiene, University of Lübeck, Lübeck, Germany.
Exp Dermatol. 2017 Dec;26(12):1253-1260. doi: 10.1111/exd.13408. Epub 2017 Nov 2.
Bullous pemphigoid (BP) is the most common of pemphigoid diseases caused by autoantibodies against the structures of dermoepidermal junction followed by complement activation, innate immune cell infiltration, neutrophil proteinase secretion and subepidermal blister formation. The first-line treatment of BP is topical and systemic glucocorticoids (GC). Regulation of the immune system and inflammatory cells is the main target of GC actions. GCs act through genomic and non-genomic mechanisms. The human glucocorticoid receptor (GR) mediates most of the biologic effects of GC: cytosolic GR binds GCs and is capable to bind to glucocorticoid response elements in DNA and either transactivate or transrepress genes depending on the tissue and cell type. In addition, GR exerts rapid, non-genomic effects possibly mediated by membrane-localized receptors or by translocation to mitochondria. GCs can also interact directly with several enzymes and cytokines. As a target treatment for BP, the production of autoantibodies should be discontinued. GCs, in spite of their wide immunosuppressive actions, are weak to stop immunoglobulin G (IgG) autoantibody formation. However, both systemic and topical GCs are able to reduce the clinical symptoms of BP. GCs are used to inhibit the secondary inflammation and symptoms, such as blistering and pruritus, and it is shown that GC treatment will gradually decrease also the autoantibody formation. Our review article analyses the mode of action of GC treatment in BP, as far it is possible due to paucity of modern immunological studies.
大疱性类天疱疮（BP）是天疱疮疾病中最常见的一种，由针对表皮与真皮交界处结构的自身抗体引起，随后补体激活、先天免疫细胞浸润、中性粒细胞蛋白酶分泌和表皮下水疱形成。BP 的一线治疗是局部和全身糖皮质激素（GC）。免疫系统和炎症细胞的调节是 GC 作用的主要靶点。GC 通过基因组和非基因组机制发挥作用。人类糖皮质激素受体（GR）介导 GC 的大多数生物学效应：胞质 GR 结合 GC，并能够结合 DNA 中的糖皮质激素反应元件，根据组织和细胞类型，要么转录激活，要么转录抑制基因。此外，GR 还可能通过膜定位受体或转位到线粒体发挥快速的非基因组作用。GC 还可以直接与几种酶和细胞因子相互作用。作为 BP 的靶向治疗，应停止产生自身抗体。尽管 GC 具有广泛的免疫抑制作用，但对于阻止免疫球蛋白 G（IgG）自身抗体的形成作用较弱。然而，全身和局部 GC 都能够减轻 BP 的临床症状。GC 用于抑制继发性炎症和症状，如水疱和瘙痒，并且已经表明 GC 治疗将逐渐减少自身抗体的形成。我们的综述文章分析了 GC 治疗 BP 的作用模式，由于现代免疫学研究的缺乏，目前还无法全面了解。
