Neuromuscul Disord. 2018 Mar;28(3):283-288. doi: 10.1016/j.nmd.2018.01.004. Epub 2018 Jan 11.

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


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.


抗HMGCR (3- hydroxy-3-methylglutary-coenzyme A reductase) 抗体は免疫介在性壊死性ミオパチーと関連するが、筋線維の変性を起こす機序は不明である。今回、抗HMGCR抗体陽性、スタチン内服歴なしの免疫介在性壊死性ミオパチー患者3人の筋病理変化を観察した。電子顕微鏡では、ミトコンドリアの変性、グリコーゲン顆粒や自己貪食性空胞を認め、自己貪食性空胞にはしばしばミトコンドリアの残存を認め、マイトファジーが示唆された。マイトファジーに関連するタンパクであるBNIP3 (upregulation of B-cell lymphoma 2/adenovirus E1B 19kD-interacting protein 3) の発現亢進や微細構造の変化は、封入対筋炎3例や多発筋炎2例、抗SRP抗体陽性免疫介在性壊死性ミオパチー3例では多くはみられなかった。これらの結果からは、抗HMGCR抗体陽性の免疫介在性壊死性ミオパチーでマイトファジーが重要な役割をしていることが示唆された。

DOI:  29402601