Mitophagy in three cases of immune-mediated necrotizing myopathy associated with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase autoantibodies: ultrastructural and immunohistochemical studies

作者：Matsubara Shiro^*; Bokuda Kota; Asano Yuri; Morishima Ryo; Sugaya Keizo; Miyamoto Kazuhito; Koide Reiji; Komori Takashi; Suzuki Shigeaki; Nishino Ichizo

来源：Neuromuscular Disorders, 2018, 28(3): 283-288.

DOI：10.1016/j.nmd.2018.01.004

• Autoantibody
• BNIP3
• HMGCR
• Mitophagy
• Necrotizing myopathy
• Programmed cell death

Immune-mediated necrotizing myopathy (IMNM) associated with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) autoantibodies occurs in patients both with and without history of statin-intake. The mechanisms of muscle fiber degeneration in this condition remain unknown. We studied pathological changes in muscle biopsies from three patients lacking history of statin-intake. Ultrastructural observations showed accumulation of degenerating mitochondria, glycogen granules and autophagic vacuoles, forming large composites in three cases, along with various nonspecific changes. The autophagic vacuoles often contained remnants of mitochondria, indicating mitophagy. Furthermore, upregulation of B-cell lymphoma 2/adenovirus E1B 19 kD-interacting protein 3 (BNIP3), a protein involved in mitophagy, was observed in two cases examined. In three cases of sporadic inclusion body myositis, two polymyositis, and three IMNM with anti-signal recognition particle antibody, BNIP3 was upregulated less frequently, and ultrastructural change of mitophagy was rarely seen. These findings suggested that mitophagy plays an important role in muscle fiber degeneration in IMNM with anti-HMGCR autoantibodies.

• 出版日期2018-3