Neuromuscular Medicine Division, Department of Neurology, Mayo Clinic, Rochester, Minnesota, 55905, USA.
Neuromuscular Medicine Division, Department of Neurology, University of Kansas Medical Center, Kansas City, Kansas, 66103, USA.
Neurotherapeutics. 2018 Oct;15(4):995-1005. doi: 10.1007/s13311-018-0658-8.
Inclusion body myositis is the most common acquired myopathy after the age of 50. It is characterized by progressive asymmetric weakness predominantly affecting the quadriceps and/or finger flexors. Loss of ambulation and dysphagia are major complications of the disease. Inclusion body myositis can be associated with cytosolic 5'-nucleotidase 1A antibodies. Muscle biopsy usually shows inflammatory cells surrounding and invading non-necrotic muscle fibers, rimmed vacuoles, congophilic inclusions, and protein aggregates. Disease pathogenesis remains poorly understood and consists of an interplay between inflammatory and degenerative pathways. Antigen-driven, clonally restricted, cytotoxic T cells represent a main feature of the inflammatory component, whereas abnormal protein homeostasis with protein misfolding, aggregation, and dysfunctional protein disposal is the hallmark of the degenerative component. Inclusion body myositis remains refractory to treatment. Better understanding of the disease pathogenesis led to the identification of novel therapeutic targets, addressing both the inflammatory and degenerative pathways.
包涵体肌炎是 50 岁以后最常见的获得性肌病。其特征是进行性非对称性无力，主要影响股四头肌和/或手指屈肌。丧失活动能力和吞咽困难是该病的主要并发症。包涵体肌炎可与胞质 5'-核苷酸酶 1A 抗体相关。肌肉活检通常显示炎性细胞围绕和侵入非坏死的肌纤维，边缘空泡，亲刚果红包涵体和蛋白聚集物。疾病发病机制仍不清楚，由炎症和退行性途径的相互作用组成。抗原驱动的、克隆受限的细胞毒性 T 细胞是炎症成分的主要特征，而异常的蛋白质动态平衡伴蛋白质错误折叠、聚集和功能失调的蛋白质处理则是退行性成分的标志。包涵体肌炎对治疗仍有抗性。对疾病发病机制的更好理解导致了新的治疗靶点的确定，既针对炎症途径又针对退行性途径。
