Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Department of Pediatric Immunology and Rheumatology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, the Netherlands.
Best Pract Res Clin Rheumatol. 2024 Sep;38(3):101976. doi: 10.1016/j.berh.2024.101976. Epub 2024 Aug 22.
Juvenile dermatomyositis is characterized by childhood-onset chronic inflammation of the muscles and skin, with potential involvement of other organs. Patients are at risk for long-term morbidity due to insufficient disease control and steroid-related toxicity. Personalised treatment is challenged by a lack of validated tools that can reliably predict treatment response and monitor ongoing (subclinical) inflammation, and by a lack of evidence regarding the best choice of medication for individual patients. A better understanding of the involved disease mechanisms could reveal potential biomarkers and novel therapeutic targets. In this review, we highlight the most relevant immune and non-immune mechanisms, elucidating the effects of interferon overexpression on tissue alongside the interplay between the interferon signature, mitochondrial function, and immune cells. We review mechanism-based biomarkers that are promising for clinical implementation, and the latest advances in targeted therapy development. Finally, we discuss key steps needed for translating these discoveries into clinical practice.
幼年特发性皮肌炎的特征是儿童期起病的肌肉和皮肤慢性炎症，可能涉及其他器官。由于疾病控制不佳和类固醇相关毒性，患者存在长期发病的风险。缺乏经过验证的工具来可靠地预测治疗反应和监测持续（亚临床）炎症，以及缺乏关于个体患者最佳药物选择的证据，使得个性化治疗面临挑战。更好地了解相关的疾病机制可能会揭示潜在的生物标志物和新的治疗靶点。在这篇综述中，我们强调了最相关的免疫和非免疫机制，阐明了干扰素过表达对组织的影响，以及干扰素特征、线粒体功能和免疫细胞之间的相互作用。我们回顾了有希望用于临床实施的基于机制的生物标志物，以及靶向治疗开发的最新进展。最后，我们讨论了将这些发现转化为临床实践所需的关键步骤。
