Seremet Teofila, Di Domizio Jeremy, Girardin Antoine, Yatim Ahmad, Jenelten Raphael, Messina Francesco, Saidoune Fanny, Schlapbach Christoph, Bogiatzi Sofia, Minisini Frederic, Garzorz-Stark Natalie, Leuenberger Matthieu, Wüthrich Héloise, Vernez Maxime, Hohl Daniel, Eyerich Stefanie, Eyerich Kilian, Guenova Emmanuella, Paul Carle, Gottardo Raphael, Conrad Curdin, Gilliet Michel
Department of Dermatology, Lausanne University Hospital CHUV and University of Lausanne, 1011, Lausanne, Switzerland.
Department of Dermatology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Nat Commun. 2024 Dec 18;15(1):10688. doi: 10.1038/s41467-024-54559-6.
Previous advances have identified immune pathways associated with inflammatory skin diseases, leading to the development of targeted therapies. However, there is a lack of molecular approaches that delineate these pathways at the individual patient level for personalized diagnostic and therapeutic guidance. Here, we conduct a cross-comparison of expression profiles from multiple inflammatory skin diseases to identify gene modules defining relevant immune pathways. Seven modules are identified, representing key immune pathways: Th17, Th2, Th1, Type I IFNs, neutrophilic, macrophagic, and eosinophilic. These modules allow the development of a molecular map with high diagnostic efficacy for inflammatory skin diseases and clinico-pathologically undetermined cases. Aligning dominant modules with treatment targets offers a rational framework for treatment selection, improving response rates in both treatment-naïve patients and non-responders to targeted therapies. Overall, our approach offers precision medicine for inflammatory skin diseases, utilizing transcriptional modules to support diagnosis and guide personalized treatment selection.
先前的进展已经确定了与炎症性皮肤病相关的免疫途径,从而推动了靶向治疗的发展。然而,缺乏在个体患者层面描绘这些途径以进行个性化诊断和治疗指导的分子方法。在此,我们对多种炎症性皮肤病的表达谱进行交叉比较,以识别定义相关免疫途径的基因模块。我们识别出了七个模块,代表关键免疫途径:Th17、Th2、Th1、I型干扰素、嗜中性粒细胞、巨噬细胞和嗜酸性粒细胞。这些模块有助于开发一种对炎症性皮肤病和临床病理诊断不明确的病例具有高诊断效能的分子图谱。将主要模块与治疗靶点相结合,为治疗选择提供了一个合理的框架,提高了初治患者和靶向治疗无反应者的反应率。总体而言,我们的方法为炎症性皮肤病提供了精准医学,利用转录模块支持诊断并指导个性化治疗选择。