Wischnewski Sven, Rausch Hans-Werner, Ikenaga Chiseko, Leipe Jan, Lloyd Thomas E, Schirmer Lucas
Department of Neurology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Department of Neurology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Mannheim Center for Translational Neuroscience, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Trends Pharmacol Sci. 2025 Mar;46(3):249-263. doi: 10.1016/j.tips.2025.01.005. Epub 2025 Feb 11.
Idiopathic inflammatory myopathies (IIMs), or myositis, are rare diseases marked by immune-driven muscle damage and complications like skin lesions and interstitial lung disease (ILD). Despite advances, challenges in diagnosis and treatment persist, particularly in inclusion body myositis (IBM), where no effective therapy exists. Recent breakthroughs, including transcriptomics and insights into antibody-mediated immunity and interferon (IFN) signaling, have clarified IIM pathophysiology and spurred the development of new therapies, such as chimeric antigen receptor (CAR) T cells and Janus kinase (JAK) inhibitors. We explore the latest findings on the mechanisms underlying adult-onset IIMs, emphasizing IBM pathobiology and its unique immune and degenerative pathways, such as a selective type 2 myofiber damage and severe cell stress. Finally, we highlight the recent advances in transcriptomics, single-cell analysis, and machine learning in transforming IIM research by improving diagnostic accuracy, uncovering therapeutic targets, and supporting the development of personalized treatment strategies.
特发性炎性肌病（IIMs），即肌炎，是一类罕见疾病，其特征为免疫驱动的肌肉损伤以及皮肤病变和间质性肺病（ILD）等并发症。尽管取得了进展，但诊断和治疗方面的挑战依然存在，尤其是在包涵体肌炎（IBM）中，目前尚无有效的治疗方法。近期的突破，包括转录组学以及对抗体介导的免疫和干扰素（IFN）信号传导的深入了解，已经阐明了IIM的病理生理学，并推动了新疗法的开发，如嵌合抗原受体（CAR）T细胞和Janus激酶（JAK）抑制剂。我们探讨了成人起病IIMs潜在机制的最新发现，重点强调了IBM的病理生物学及其独特的免疫和退行性途径，如选择性2型肌纤维损伤和严重的细胞应激。最后，我们强调了转录组学、单细胞分析和机器学习在通过提高诊断准确性、揭示治疗靶点以及支持个性化治疗策略的开发来改变IIM研究方面的最新进展。
