Pathomechanisms of anti–cytosolic 5′‐nucleotidase 1<scp>A</scp> autoantibodies in sporadic inclusion body myositis

Tawara, Nozomu; Yamashita, Satoshi; Zhang, Xiao; Korogi, M.; Zhang, Ziwei; Doki, T.; Matsuo, Yoshimasa; Nakane, Shunya; Maeda, Yasushi; Sugie, Kazuma; Suzuki, Naoki; Akiyama, Masashi; Ando, Yumiko

doi:10.1002/ana.24919

Cited by 62 publications

(79 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, we found that p62 was significantly upregulated in anti‐cN1A‐positive sIBM IgG‐supplemented cells in an in vitro passive immunization model . Similar p62‐positive sarcoplasmic aggregates were observed in the myofibers of anti‐cN1A‐positive sIBM IgG‐injected mice in an in vivo passive immunization model . We also found that cN1A expression levels were reduced in the muscle tissues of patients with sIBM that is associated with anti‐cN1A autoantibodies, as well as in lysates from the antibody‐positive IgG‐supplemented cells.…”

Section: Pathogenesis In Sibmsupporting

confidence: 69%

“…The pathogenic role of anti‐cN1A autoantibodies has not been fully investigated. However, we found that p62 was significantly upregulated in anti‐cN1A‐positive sIBM IgG‐supplemented cells in an in vitro passive immunization model . Similar p62‐positive sarcoplasmic aggregates were observed in the myofibers of anti‐cN1A‐positive sIBM IgG‐injected mice in an in vivo passive immunization model .…”

Section: Pathogenesis In Sibmsupporting

confidence: 68%

“…With regard to the clinicopathological features of sIBM patients with anti‐cN1A autoantibodies, an initial study suggested that seropositivity for the anti‐cN1A autoantibodies was associated with greater motor and functional disability: sIBM patients with the autoantibodies showed more prominent bulbar, facial and respiratory symptoms . In our investigation, the percentage of patients with hepatitis C virus antibodies was significantly lower, and the mean area of type 2 myofibers was significantly smaller in the anti‐cN1A‐positive group compared with the autoantibody‐negative group . A recent retrospective study of 311 sIBM patients showed that the anti‐cN1A‐positive patients had a higher adjusted mortality risk, lower frequency of proximal upper limb weakness at disease onset and an increased prevalence of excess cytochrome oxidase‐deficient myofibers in muscle biopsy samples .…”

Section: Pathogenesis In Sibmmentioning

confidence: 49%

“…As cN1A is an aggregation‐prone protein, the aggregated protein might be presented as an autoantigen under pathological conditions, leading to production of the autoantibodies. Our group established a novel cell‐based assay for the detection of the autoantibodies, which had apparently equivalent sensitivity and better specificity for the diagnosis of sIBM, compared with the previously described methods . In order to establish the usefulness of measuring anti‐cN1A autoantibodies to facilitate a more accurate diagnosis of sIBM, additional research is required to standardize antibody detection methods, along with consideration of the epitopes recognized by the antibodies and the immunoglobulin isotypes.…”

Section: Diagnosismentioning

confidence: 99%

See 3 more Smart Citations

Anti‐NT5C1A autoantibodies for the diagnosis and study of the pathogenesis of sporadic inclusion body myositis

Yamashita

Tawara

Ando

2017

Clinical & Exp Neuroim

Self Cite

View full text Add to dashboard Cite

Sporadic inclusion body myositis (sIBM) is a chronic and progressive inflammatory myopathy that is commonest in the population aged >50 years. Asymmetric muscle weakness and wasting of the quadriceps, and finger and wrist flexor muscles are characteristic of sIBM. Histological findings for sIBM are characterized by a combination of inflammatory and myodegenerative pathologies. The pathogenesis of sIBM is not yet fully understood, and serum markers have not been identified for diagnosis of the disease or assessment of therapeutic efficacy. Recently, autoantibodies against cytosolic 5 0 -nucleotidase 1A have been identified in plasma and serum samples from patients with sIBM. Various methods with clinical utility have been established to detect anti-cN1A autoantibodies for the diagnosis of sIBM. Importantly, the autoantibodies might have direct roles in the development of the disease by causing dysfunction in proteasomal and lysosomal degradation. Future studies should be carried out to elucidate the molecular mechanisms by which the sarcoplasmic autoantigen is recognized and involved in the degeneration of myofibers. Additional research is essential to provide a better understanding of the relationship between the inflammatory and degenerative processes of sIBM. EpidemiologyGenerally, sIBM is the commonest acquired myopathy in older individuals, and males are more commonly affected than females (3:1). Its prevalence varies among countries and ethnic groups. The

show abstract

Section: Pathogenesis In Sibmsupporting

confidence: 69%

Section: Pathogenesis In Sibmsupporting

confidence: 68%

Section: Pathogenesis In Sibmmentioning

confidence: 49%

Section: Diagnosismentioning

confidence: 99%

See 2 more Smart Citations

Anti‐NT5C1A autoantibodies for the diagnosis and study of the pathogenesis of sporadic inclusion body myositis

Yamashita

Tawara

Ando

2017

Clinical & Exp Neuroim

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, it might help differentiate between myositis subgroups. In a recent study, the pathogenic role of anti-cN1A in IBM was demonstrated both in vivo and in an in vitro passive immunization model suggesting that the autoantibody might affect protein degradation in myofibers [106].…”

Section: Other Autoantibodiesmentioning

confidence: 99%

Clinical significance of myositis-specific autoantibodies

Nakashima

2018

Immunological Medicine

View full text Add to dashboard Cite

To date, increasing numbers of myositis-specific autoantibodies (MSAs) have been reported and their clinical significance has been elucidated. Anti-aminoacyl-tRNA synthetase (ARS) and anti-melanoma-differentiation associated gene 5 (MDA5) are strongly associated with interstitial lung disease (ILD); however, the clinical course of ILD is different depending on which autoantibody is present. Anti-ARS is associated with chronic and repetitive ILD and anti-MDA5 is associated with rapidly progressive ILD. Anti-MDA5, anti-transcriptional intermediary factor (TIF) 1-c, anti-nuclear matrix protein (NXP) 2 and anti-Mi-2 antibodies are dermatomyositis specific. Anti-TIF1-c and anti-NXP-2 antibodies are associated with malignancy, and anti-signal recognition particle (SRP) and anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies are associated with immune-mediated necrotizing myopathy (IMNM). Prognosis is also different among MSA-positive patient groups. Thus, MSAs are of great use for predicting disease course, prognosis, and determining therapeutic strategy as well as the diagnosis of idiopathic inflammatory myopathy (IIM) patients. Investigation of the pathogenic role of MSAs and their corresponding autoantigens will help us to understand the pathophysiology of IIM and identify new therapeutic targets. ARTICLE HISTORY

show abstract

Immune and myodegenerative pathomechanisms in inclusion body myositis

Keller

Schmidt

Lünemann

2017

Ann Clin Transl Neurol

View full text Add to dashboard Cite

Inclusion Body Myositis (IBM) is a relatively common acquired inflammatory myopathy in patients above 50 years of age. Pathological hallmarks of IBM are intramyofiber protein inclusions and endomysial inflammation, indicating that both myodegenerative and inflammatory mechanisms contribute to its pathogenesis. Impaired protein degradation by the autophagic machinery, which regulates innate and adaptive immune responses, in skeletal muscle fibers has recently been identified as a potential key pathomechanism in IBM. Immunotherapies, which are successfully used for treating other inflammatory myopathies lack efficacy in IBM and so far no effective treatment is available. Thus, a better understanding of the mechanistic pathways underlying progressive muscle weakness and atrophy in IBM is crucial in identifying novel promising targets for therapeutic intervention. Here, we discuss recent insights into the pathomechanistic network of mutually dependent inflammatory and degenerative events during IBM.

show abstract

Pathomechanisms of anti–cytosolic 5′‐nucleotidase 1A autoantibodies in sporadic inclusion body myositis

Cited by 62 publications

References 24 publications

Anti‐NT5C1A autoantibodies for the diagnosis and study of the pathogenesis of sporadic inclusion body myositis

Anti‐NT5C1A autoantibodies for the diagnosis and study of the pathogenesis of sporadic inclusion body myositis

Clinical significance of myositis-specific autoantibodies

Immune and myodegenerative pathomechanisms in inclusion body myositis

Contact Info

Product

Resources

About