Centre for Rare Autoimmune and Autoinflammatory Diseases (ERN-ReCONNET), Department of Rheumatology, Emergency Clinical County Hospital Cluj, 400347 Cluj-Napoca, Romania.
CMI Reumatologie Dr. Damian, 6-8 Petru Maior St., 400002 Cluj-Napoca, Romania.
Int J Mol Sci. 2022 Jul 1;23(13):7358. doi: 10.3390/ijms23137358.
Inclusion body myositis (IBM) is an acquired, late-onset inflammatory myopathy, with both inflammatory and degenerative pathogenesis. Although idiopathic inflammatory myopathies may be associated with malignancies, IBM is generally not considered paraneoplastic. Many studies of malignancy in inflammatory myopathies did not include IBM patients. Indeed, IBM is often diagnosed only after around 5 years from onset, while paraneoplastic myositis is generally defined as the co-occurrence of malignancy and myopathy within 1 to 3 years of each other. Nevertheless, a significant association with large granular lymphocyte leukemia has been recently described in IBM, and there are reports of cancer-associated IBM. We review the pathogenic mechanisms supposed to be involved in IBM and outline the common mechanisms in IBM and malignancy, as well as the therapeutic perspectives. The terminally differentiated, CD8+ highly cytotoxic T cells expressing NK features are central in the pathogenesis of IBM and, paradoxically, play a role in some cancers as well. Interferon gamma plays a central role, mostly during the early stages of the disease. The secondary mitochondrial dysfunction, the autophagy and cell cycle dysregulation, and the crosstalk between metabolic and mitogenic pathways could be shared by IBM and cancer. There are intermingled subcellular mechanisms in IBM and neoplasia, and probably their co-existence is underestimated. The link between IBM and cancers deserves further interest, in order to search for efficient therapies in IBM and to improve muscle function, life quality, and survival in both diseases.
包涵体肌炎(IBM)是一种获得性、迟发性炎性肌病,具有炎症和退行性发病机制。虽然特发性炎性肌病可能与恶性肿瘤相关,但 IBM 通常不被认为是副肿瘤性的。许多关于炎性肌病中恶性肿瘤的研究并未包括 IBM 患者。事实上,IBM 通常在发病后约 5 年才被诊断出来,而副肿瘤性肌炎通常被定义为恶性肿瘤和肌病在彼此 1 到 3 年内同时发生。然而,最近在 IBM 中描述了与大颗粒淋巴细胞白血病的显著相关性,并且有癌症相关 IBM 的报道。我们回顾了假定参与 IBM 的发病机制,并概述了 IBM 和恶性肿瘤之间的常见机制,以及治疗前景。表达 NK 特征的终末分化、CD8+高细胞毒性 T 细胞在 IBM 的发病机制中起核心作用,但在某些癌症中也起作用。干扰素γ起核心作用,主要在疾病的早期阶段。继发性线粒体功能障碍、自噬和细胞周期失调,以及代谢和有丝分裂途径之间的串扰,可能是 IBM 和癌症共有的。IBM 和肿瘤存在混杂的亚细胞机制,可能它们的共存被低估了。IBM 和癌症之间的联系值得进一步关注,以便在 IBM 中寻找有效的治疗方法,并改善两种疾病的肌肉功能、生活质量和生存。