Clinicopathologic features of myositis patients with CD8-MHC-1 complex pathology

Ikenaga, Chiseko; Kubota, Akatsuki; Kadoya, Masato; Taira, Kenichiro; Uchio, Naohiro; Hida, Ayumi; Maeda, Mitsuaki; Nagashima, Yu; Ishiura, Hiroyuki; Kaida, Kenichi; Goto, Jun; Tsuji, Shoji; Shimizu, Jun

doi:10.1212/wnl.0000000000004333

Cited by 32 publications

(31 citation statements)

References 25 publications

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“…The histological picture encompasses “invasion” of muscle fibers by endomysial cytotoxic CD8 + T-cells, widespread and moderate to strong upregulation of MHC class I, signs of protein accumulation by detection of amyloid (Congo red, thioflavin S, immunohistochemistry for p62 or TDP-43), detection of tubulofilaments on EM, vacuoles and signs of mitochondrial damage as evidenced by histochemical proof of COX-deficient muscle fibers, and paracristallin inclusions [ 2, 59 ]. However, signs of protein accumulation can be absent, even the “canonical” feature of rimmed vacuoles can be missing [ 25, 26 ].…”

Section: Clinical Presentation Auto-antibodies and Muscle Histopathomentioning

confidence: 99%

Current Classification and Management of Inflammatory Myopathies

Schmidt

2018

JND

225

199

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Inflammatory disorders of the skeletal muscle include polymyositis (PM), dermatomyositis (DM), (immune mediated) necrotizing myopathy (NM), overlap syndrome with myositis (overlap myositis, OM) including anti-synthetase syndrome (ASS), and inclusion body myositis (IBM). Whereas DM occurs in children and adults, all other forms of myositis mostly develop in middle aged individuals. Apart from a slowly progressive, chronic disease course in IBM, patients with myositis typically present with a subacute onset of weakness of arms and legs, often associated with pain and clearly elevated creatine kinase in the serum. PM, DM and most patients with NM and OM usually respond to immunosuppressive therapy, whereas IBM is largely refractory to treatment. The diagnosis of myositis requires careful and combinatorial assessment of (1) clinical symptoms including pattern of weakness and paraclinical tests such as MRI of the muscle and electromyography (EMG), (2) broad analysis of auto-antibodies associated with myositis, and (3) detailed histopathological work-up of a skeletal muscle biopsy. This review provides a comprehensive overview of the current classification, diagnostic pathway, treatment regimen and pathomechanistic understanding of myositis.

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Section: Clinical Presentation Auto-antibodies and Muscle Histopathomentioning

confidence: 99%

Current Classification and Management of Inflammatory Myopathies

Schmidt

2018

JND

225

199

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“…FLNC, SQSTM1, ZASP, and BAG3 are known to be mutated in rare inherited vacuolar myopathies and also play integral roles in the autophagy pathway [36–38]. SQSTM1 (Sequestosome 1, also known as p62) is a ubiquitin-binding autophagy adaptor that has been shown to label protein inclusions in IBM muscle [39–41]. The two rare variants identified in VCP were previously reported as putative disease-associated variants [31,42,43], and expression of these variants in cell culture causes an accumulation of the autophagosome markers p62 and LC3-II, suggestive of a disruption in autophagy [44].…”

Section: Proteostasismentioning

confidence: 99%

New Developments in the Genetics of Inclusion Body Myositis

2018

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In a study of 252 IBM patients, the class II MHC allele HLA-DRB1*03:01 showed the most significant association with IBM, and that risk could be largely attributed to amino acids within the peptide-binding pocket. Candidate gene sequencing identified rare missense variants in proteins regulating protein homeostasis including VCP and SQSTM1. An unbiased approach employing exome sequencing of genes encoding rimmed vacuole proteins identified FYCO1 variants in IBM. Ongoing GWAS approaches may shed new light on genetic risk factors for IBM. Many variants have been reported at an increased frequency in IBM in small studies; however, only HLA association has shown genome-wide significance. Future studies are needed to validate variants in larger cohorts and to understand the molecular roles these risk factors play in IBM.

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“…In the histopathological hallmarks, the distribution and the immunophenotypic profile of the inflammatory cells are similar to those seen in polymyositis macrophages and CD8+ T cells which invade nonnecrotic muscle fibers that express MHC class I antigen on the sarcolemma [33], signs of protein accumulation by detection of amyloid (Congo red, thioflavin S, immunohistochemistry for p62 or TDP-43), detection of tubulofilaments on EM, vacuoles and signs of mitochondrial damage as evidenced by histochemical proof of COX-deficient muscle fibers, and paracrystalline inclusions [3,34,35].…”

Section: Inclusion Body Myositismentioning

confidence: 68%

Inflammatory Muscle Diseases

Sumida¹,

Chiba²,

Mattera³

2020

Muscle Cells - Recent Advances and Future Perspectives

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Inflammatory myopathies, also called idiopathic inflammatory myopathy or myositis, are rare conditions characterized by the involvement of various organs in addition to muscle tissue. These changes can lead to severe impairments and adversely impact the quality of life of affected individuals. The diagnosis and treatment of inflammatory myopathies involve the participation of an interdisciplinary team, due to the complexity of the disease and the high variety of possible signs and symptoms. In this chapter we will discuss the epidemiology and characteristics of the main subtypes of inflammatory myopathies, such as polymyositis, dermatomyositis, necrotizing myopathy, overlap myositis, and myositis of inclusion bodies. Next, we will discuss the existence of crosstalk between inflammatory processes in the oral cavity and their consequences on skeletal muscle. As oral inflammation can increase infiltration of macrophages in muscle tissue and this increase is related to the production of proinflammatory cytokines in this tissue, these cytokines can cause muscle weakness. It is important to consider the prevention of chronic inflammatory processes in order to maintain muscle integrity or even prevent the worsening of the clinical condition of patients with inflammatory muscle diseases.

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Clinicopathologic features of myositis patients with CD8-MHC-1 complex pathology

Abstract: CD8-MHC-1 complex is present in patients with PM, IBM, or unclassifiable group. The data may serve as an argument for a trial of immunosuppressive treatment in p62-immunonegative patients with unclassifiable myositis.

Cited by 32 publications

References 25 publications

Current Classification and Management of Inflammatory Myopathies

Current Classification and Management of Inflammatory Myopathies

New Developments in the Genetics of Inclusion Body Myositis

Inflammatory Muscle Diseases

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