Autophagy markers LC3 and p62 accumulate in immune‐mediated necrotizing myopathy

Girolamo, Francesco; Lia, Annamaria; Annese, Tiziana; Giannini, Margherita; Amati, A; D’Abbicco, Dario; Tampoia, Marilina; Virgintino, Daniela; Ribatti, Doménico; Serlenga, L; Iannone, Florenzo; Trojano, María

doi:10.1002/mus.26608

Cited by 31 publications

(24 citation statements)

References 50 publications

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“…Autophagy mediates the transfer of damaged proteins and intracellular organelles to the lysosomes [20]. Activated autophagolysosomal pathways had been described in NAM biopsy samples [21][22][23]. Similarly, autophagy markers p62/SQSTM1 accumulation further increased p62/SQSTM1 expression in the cardiac tissue, implying that autophagy dysfunction might play a role in the pathogenesis of cardiac disorders in NAM.…”

Section: Discussionmentioning

confidence: 96%

Immunotherapy reversed myopathy but not cardiomyopathy in a necrotizing autoimmune myopathy patient with positive anti-SRP and MDA-5 autoantibodies

et al. 2021

BMC Cardiovasc Disord

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Background Necrotizing autoimmune myopathy (NAM) is pathologically characterized by myofiber necrosis and regeneration with paucity or absence of inflammatory cells in muscle biopsy. Two autoantibodies, namely anti-signal recognition particle (SRP)-antibodies and anti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR)-antibodies, are typically specific with NAM. Anti-SRP-positive NAM can be associated with cardiomyopathy which responds well to immunotherapy. Here we reported an anti-SRP-antibody and anti-MDA5-antibody NAM patient who developed severe cardiomyopathy after gaining significant improvement of myopathy and subsequently accepted heart transplantation. Case presentation A NAM case with both positive anti-SRP and MDA-5 antibodies who gained significant improvement of the skeletal muscle weakness with immunotherapy, but 3 years later he developed severe dilated cardiomyopathy and at last received heart transplantation. Myocardial biopsy showed disarranged and atrophic myofibers, remarkable interstitial fibrosis without inflammatory infiltrates. Immunohistochemistry analysis revealed increased polyubiquitin-binding protein p62/SQSTM1 protein expression and the positive staining of cleaved-caspase 3 in a few cardiomyocytes. After the transplantation, the patient was symptom-free on oral prednisone (10 mg/day) and tacrolimus (2 mg/day). Conclusions We described the first case of anti-SRP and anti-MAD5 positive NAM who had received heart transplantation because of cardiopathy. Though the myopathy had been clinically improved after immunotherapy, the cardiomyopathy remained progressive and lethal. The processes of dysfunctional autophagy and augmented apoptosis were putatively pathophysiological mechanisms underlying cardiac damage in anti-SRP and anti-MAD5 positive NAM.

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Section: Discussionmentioning

confidence: 96%

Immunotherapy reversed myopathy but not cardiomyopathy in a necrotizing autoimmune myopathy patient with positive anti-SRP and MDA-5 autoantibodies

et al. 2021

BMC Cardiovasc Disord

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“…In addition to IBM, autophagy activation could also be detected in PM, DM and IMNM muscle tissues, whereas the autophagic activation, modulation and interaction with the immune system, are different in each type of IIM ( 60 , 71 , 72 ). In IBM, lysosomal enzymes Cathepsin B and D, are inhibited, while in PM, their activities were actually increased ( 55 ).…”

Section: Autophagy and Autophagic Cell Deathmentioning

confidence: 99%

Programmed Cell Death Pathways in the Pathogenesis of Idiopathic Inflammatory Myopathies

et al. 2021

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Idiopathic inflammatory myopathy (IIM) is a heterogeneous group of acquired, autoimmune muscle diseases characterized by muscle inflammation and extramuscular involvements. Present literatures have revealed that dysregulated cell death in combination with impaired elimination of dead cells contribute to the release of autoantigens, damage-associated molecular patterns (DAMPs) and inflammatory cytokines, and result in immune responses and tissue damages in autoimmune diseases, including IIMs. This review summarizes the roles of various forms of programmed cell death pathways in the pathogenesis of IIMs and provides evidence for potential therapeutic targets.

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“…UPR signaling protects cells or induces cell death by regulating autophagy under extreme conditions (Song et al, 2017). A previous study revealed chaperone-assisted selective autophagy in IMNM (Fischer et al, 2019;Girolamo et al, 2019). However, whether the activation of ER stress-induced autophagy pathways is involved in IMNM and other IIM subtypes remains elusive.…”

Section: Introductionmentioning

confidence: 99%

Endoplasmic Reticulum Stress Is Involved in Muscular Pathogenesis in Idiopathic Inflammatory Myopathies

Gao

Zhang

et al. 2022

Front. Cell Dev. Biol.

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Objectives: Endoplasmic reticulum (ER) stress plays pivotal roles in the regulation of skeletal muscle damage and dysfunction in multiple disease conditions. We postulate the activation of ER stress in idiopathic inflammatory myopathies (IIM).Methods: Thirty-seven patients with immune-mediated necrotizing myopathy (IMNM), 21 patients with dermatomyositis (DM), 6 patients with anti-synthetase syndrome (ASS), and 10 controls were enrolled. The expression of ER stress-induced autophagy pathway was detected using histological sections, Western blot, and real-time quantitative Polymerase Chain Reaction.Results: ER stress-induced autophagy pathway was activated in biopsied muscle of patients with IMNM, DM, and ASS. The ER chaperone protein, glucose-regulated protein 78 (GRP78)/BiP expression in skeletal muscle correlated with autophagy, myofiber atrophy, myonecrosis, myoregeneration, and disease activity in IMNM.Conclusion: ER stress was involved in patients with IIM and correlates with disease activity in IMNM. ER stress response may be responsible for skeletal muscle damage and repair in IIM.

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Autophagy markers LC3 and p62 accumulate in immune‐mediated necrotizing myopathy

Cited by 31 publications

References 50 publications

Immunotherapy reversed myopathy but not cardiomyopathy in a necrotizing autoimmune myopathy patient with positive anti-SRP and MDA-5 autoantibodies

Immunotherapy reversed myopathy but not cardiomyopathy in a necrotizing autoimmune myopathy patient with positive anti-SRP and MDA-5 autoantibodies

Programmed Cell Death Pathways in the Pathogenesis of Idiopathic Inflammatory Myopathies

Endoplasmic Reticulum Stress Is Involved in Muscular Pathogenesis in Idiopathic Inflammatory Myopathies

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