TY - JOUR
T1 - Mitophagy in three cases of immune-mediated necrotizing myopathy associated with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase autoantibodies
T2 - ultrastructural and immunohistochemical studies
AU - Matsubara, Shiro
AU - Bokuda, Kota
AU - Asano, Yuri
AU - Morishima, Ryo
AU - Sugaya, Keizo
AU - Miyamoto, Kazuhito
AU - Koide, Reiji
AU - Komori, Takashi
AU - Suzuki, Shigeaki
AU - Nishino, Ichizo
N1 - Publisher Copyright:
© 2018 Elsevier B.V.
PY - 2018/3
Y1 - 2018/3
N2 - 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.
AB - 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.
KW - Autoantibody
KW - BNIP3
KW - HMGCR
KW - Mitophagy
KW - Necrotizing myopathy
KW - Programmed cell death
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U2 - 10.1016/j.nmd.2018.01.004
DO - 10.1016/j.nmd.2018.01.004
M3 - Article
C2 - 29402601
AN - SCOPUS:85041287493
SN - 0960-8966
VL - 28
SP - 283
EP - 288
JO - Neuromuscular Disorders
JF - Neuromuscular Disorders
IS - 3
ER -