PDF(Pubmed)
Abstract：
Pityriasis rubra pilaris (PRP) is a rare inflammatory skin disease with a poorly understood pathogenesis. Through a molecularly driven precision medicine approach and an extensive mechanistic pathway analysis in PRP skin samples, compared to psoriasis, atopic dermatitis, healed PRP, and healthy controls, we identified IL-1β as a key mediator, orchestrating an NF-κB-mediated IL-1β-CCL20 axis, including activation of CARD14 and NOD2. Treatment of three patients with the IL-1 antagonists anakinra and canakinumab resulted in rapid clinical improvement and reversal of the PRP-associated molecular signature with a 50% improvement in skin lesions after 2 to 3 weeks. This transcriptional signature was consistent with in vitro stimulation of keratinocytes with IL-1β. With the central role of IL-1β underscoring its potential as a therapeutic target, our findings propose a redefinition of PRP as an autoinflammatory keratinization disorder. Further clinical trials are needed to validate the efficacy of IL-1β antagonists in PRP.
摘要：
毛发发红糠疹(PRP)是一种罕见的炎症性皮肤病,其发病机制尚不清楚。通过分子驱动的精准医学方法和PRP皮肤样品中广泛的机械途径分析，与牛皮癣相比，特应性皮炎,治愈的PRP,和健康的控制，我们确定IL-1β为关键介质，协调NF-κB介导的IL-1β-CCL20轴，包括CARD14和NOD2的激活。用IL-1拮抗剂anakinra和canakinumab治疗三名患者导致快速的临床改善和PRP相关分子特征的逆转，2至3周后皮肤病变改善50％。该转录特征与用IL-1β体外刺激角质形成细胞一致。由于IL-1β的核心作用强调了其作为治疗靶点的潜力，我们的研究结果提出了将PRP重新定义为自身炎症性角质化疾病.需要进一步的临床试验来验证IL-1β拮抗剂在PRP中的功效。
