Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
Department of Dermatology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
J Dermatol Sci. 2024 Apr;114(1):44-51. doi: 10.1016/j.jdermsci.2024.03.001. Epub 2024 Mar 6.
Bullous pemphigoid (BP) is an antibody-mediated blistering disease predominantly affecting the elderly. The pathogenesis involves both complement-dependent and complement-independent mechanisms. The therapeutic potential of targeting complement-independent mechanism has not yet been determined. The mainstay of treatment, corticosteroid, has many side effects, indicating the needs of better treatments.
We tempted to establish an in vitro model of BP which resembles complement-independent mechanism and to examine the therapeutic potential of a novel anti-inflammatory agent, diacerein.
Cultured HaCaT cells were treated with purified antibodies from BP patients, with or without diacerein to measure the cell interface presence of BP180, protein kinase C, and the production of proinflammatory cytokines. An open-label, randomized, phase 2 trial was conducted to compare topical diacerein and clobetasol ointments in patients with mild-to-moderate BP (NCT03286582).
The reduced presentation of BP180 at cell interface after treating with BP autoantibodies was noticed in immunofluorescence and western blotting studies. The phenomenon was restored by diacerein. Diacerein also reduced the autoantibody-induced increase of pro-inflammatory cytokines. Reciprocal changes of BP180 and protein kinase C at the cell interface were found after treating with BP autoantibodies. This phenomenon was also reversed by diacerein in a dose-dependent manner. The phase 2 trial showed that topical diacerein reduced the clinical symptoms which were comparable to those of topical clobetasol.
Diacerein inhibited BP autoantibody-induced reduction of BP180 and production of proinflammatory cytokines in vitro and showed therapeutic potential in patients with BP. It is a novel drug worthy of further investigations.
大疱性类天疱疮（BP）是一种主要影响老年人的抗体介导的水疱性疾病。发病机制涉及补体依赖性和非依赖性机制。针对非补体依赖性机制的治疗潜力尚未确定。治疗的主要手段是皮质类固醇，它有许多副作用，表明需要更好的治疗方法。
我们试图建立一种类似于非补体依赖性机制的 BP 体外模型，并研究新型抗炎药二乙酰瑞林的治疗潜力。
用 BP 患者的纯化抗体处理培养的 HaCaT 细胞，有或没有二乙酰瑞林，以测量 BP180、蛋白激酶 C 和促炎细胞因子的产生。进行了一项开放标签、随机、2 期临床试验，比较了轻度至中度 BP 患者的外用二乙酰瑞林和卤倍他索软膏（NCT03286582）。
免疫荧光和 Western blot 研究发现，用 BP 自身抗体处理后，细胞界面上 BP180 的表达减少。二乙酰瑞林可恢复这种现象。二乙酰瑞林还降低了自身抗体诱导的促炎细胞因子的增加。在用 BP 自身抗体处理后，在细胞界面上发现了 BP180 和蛋白激酶 C 的相互变化。二乙酰瑞林以剂量依赖性方式逆转了这种现象。2 期临床试验表明，外用二乙酰瑞林可减轻临床症状，与外用卤倍他索相当。
二乙酰瑞林抑制了 BP 自身抗体诱导的 BP180 减少和促炎细胞因子的产生，在 BP 患者中显示出治疗潜力。它是一种值得进一步研究的新型药物。
