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Accumulation of autophagosome cargo protein p62 is common in idiopathic inflammatory myopathies


1, 2, 3, 4, 5, 6, 7, 8, 9, 10

 

  1. Muscle Research Unit, Internal Medicine Service, Hospital Clínic de Barcelona, Universidad de Barcelona and CIBERER, Barcelona, Spain.
  2. Muscle Disease Unit, Laboratory of Muscle Stem Cells and Gene Regulations, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; and Faculty of Computer Science, Multimedia and Telecommunications and Faculty of Health Sciences, Universitat Oberta de Catalunya, Barcelona, Spain.
  3. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  4. Muscle Research Unit, Internal Medicine Service, Hospital Clínic de Barcelona, Universidad de Barcelona and CIBERER, Barcelona, Spain.
  5. Enviromental Autoimmunity Group, National Institute of Environmental Health Sciences, National Institutes of Health, Bethesda, MD, USA.
  6. Vall d’Hebron Hospital and Autonomous University of Barcelona, Spain.
  7. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  8. Departments of Neurology and Neuropathology, Charité-Universitätsmedizin, Berlin, Germany.
  9. Muscle Disease Unit, Laboratory of Muscle Stem Cells and Gene Regulations, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; and Vall d’Hebron Hospital and Autonomous University of Barcelona, Spain.
  10. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. acorse@jhmi.edu

CER13081
2021 Vol.39, N°2
PI 0351, PF 0356
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PMID: 32896253 [PubMed]

Received: 06/01/2020
Accepted : 20/04/2020
In Press: 01/09/2020
Published: 09/04/2021

Abstract

OBJECTIVES:
The subsarcolemmal accumulation of p62 aggregates in myofibres has been proposed to be characteristic of sporadic inclusion body myositis (sIBM). The objective of this study was to analyse the patterns and prevalence of p62 immunostaining and to quantitate p62 gene expression in muscle biopsies from a large number of patients with different types of myopathic and neurogenic disorders.
METHODS:
For the p62 immunostaining analysis, all patients with a muscle biopsy immunostained for p62 at the Johns Hopkins Neuromuscular Pathology Laboratory from 2013 to 2017 were included (n=303). The prevalence and pattern of p62 immunostaining were compared between patients with histologically normal muscle (n=29), inflammatory myopathies (n=136), non-inflammatory myopathies (n=53), and neurogenic disorders (n=85). p62 expression levels were analysed using an existing RNAseq dataset including data from dermatomyositis (DM; n=39), immune-mediated necrotising myopathy (IMNM; n=49), antisynthetase syndrome (AS; n=18), and sIBM (n=23) patients as well as 20 histologically normal muscle biopsies.
RESULTS:
p62 staining was absent in normal biopsies, but present in biopsies from those with polymyositis (29%), non-inflammatory myopathies (all <31%), neurogenic disorders (31%), dermatomyositis (57%), sIBM (92%) and IMNM (87%). In all diseases studied, p62 accumulation was more prevalent in biopsies with more severe muscle damage. sIBM biopsies had decreased p62 expression levels compared to the other groups (corrected p<0.04).
CONCLUSIONS:
p62 accumulation is a general response to muscle injury and not a specific marker for sIBM. Also, in sIBM, p62 RNA levels are decreased, suggesting that, in this disease, p62 aggregation is not due to overexpression.

Rheumatology Article