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Clusterin is upregulated in serum and muscle tissue in idiopathic inflammatory myopathies and associates with clinical disease activity and cytokine profile


1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19

 

  1. Institute of Rheumatology, Prague, and Department of Rheumatology, First Faculty of Medicine, Charles University, Prague, Czech Republic.
  2. Institute of Rheumatology, Prague, Czech Republic. vernerova@revma.cz
  3. Institute of Rheumatology, Prague, and Department of Rheumatology, First Faculty of Medicine, Charles University, Prague, Czech Republic.
  4. Institute of Rheumatology, Prague, and Faculty of Science, Charles University, Prague, Czech Republic.
  5. Institute of Rheumatology, Prague, Czech Republic.
  6. Institute of Rheumatology, Prague, and Department of Rheumatology, First Faculty of Medicine, Charles University, Prague, Czech Republic.
  7. Institute of Rheumatology, Prague, and Department of Rheumatology, First Faculty of Medicine, Charles University, Prague, Czech Republic.
  8. Institute of Rheumatology, Prague, and Department of Physiotherapy, Faculty of Physical Education and Sport, Charles University, Prague, Czech Republic.
  9. Institute of Rheumatology, Prague, Czech Republic 4 Department of Physiotherapy, Faculty of Physical Education and Sport, Charles University, Prague, Czech Republic
  10. Institute of Rheumatology, Prague, and Department of Rheumatology, First Faculty of Medicine, Charles University, Prague, Czech Republic.
  11. Institute of Rheumatology, Prague, Czech Republic.
  12. Institute of Rheumatology, Prague, and Department of Rheumatology, First Faculty of Medicine, Charles University, Prague, Czech Republic.
  13. Institute of Rheumatology, Prague, and Department of Rheumatology, First Faculty of Medicine, Charles University, Prague, Czech Republic.
  14. Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia.
  15. Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, and Institute of Pathophysiology, Faculty of Medicine, Comenius University, Bratislava, Slovakia.
  16. Department of Pathology and Molecular Medicine, 2nd Medical School and University Hospital Motol, Charles University, Prague, Czech Republic.
  17. Institute of Rheumatology, Prague, and Department of Rheumatology, First Faculty of Medicine, Charles University, Prague, Czech Republic.
  18. Institute of Rheumatology, Prague, and Department of Rheumatology, First Faculty of Medicine, Charles University, Prague, Czech Republic.
  19. Institute of Rheumatology, Prague, and Department of Rheumatology, First Faculty of Medicine, Charles University, Prague, Czech Republic.

CER13297
2021 Vol.39, N°5
PI 1021, PF 1032
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PMID: 33124569 [PubMed]

Received: 09/03/2020
Accepted : 07/09/2020
In Press: 29/10/2020
Published: 31/08/2021

Abstract

OBJECTIVES:
The aim of this cross-sectional study was to explore the circulating and skeletal muscle expression of clusterin (CLU) in inflammatory myopathies (IIM) and its potential implication in pathogenetic mechanisms of the disease.
METHODS:
A total of 85 IIM patients and 86 healthy controls (HC) were recruited. In addition, 20 IIM patients and 21 HC underwent a muscle biopsy. Circulating CLU was measured by ELISA. Serum cytokine profile of patients and HC was assessed by Cytokine 27-plex Assay. Immunohistochemical localisation of CLU was assessed in 10 IIM and 4 control muscle tissue specimens. The expression of CLU and myositis related cytokines in muscle was determined by qPCR.
RESULTS:
Serum levels of CLU were significantly increased in IIM patients compared to controls (86.2 (71.6–99.0) vs. 59.6 (52.6–68.4) μg/mL, p<0.0001) and positively correlated with myositis disease activity assessment (MYOACT) (r=0.337, p=0.008), myositis intention-to-treat activity index (MITAX) (r=0.357, p=0.004) and global disease assessment evaluated by physician (r=0.309, p=0.015). Moreover, serum CLU correlated with cytokines and chemokines involved in IIM and their combined effect on disease activity was revealed by multivariate redundancy analysis. In muscle tissue, CLU mRNA was increased in IIM patients compared to controls (p=0.032) and CLU accumulated in the cytoplasm of regenerating myofibres.
CONCLUSIONS:
We suggest that the up-regulation of clusterin in circulation and skeletal muscle of IIM patients may be an inflammation and atrophy induced response of the organism intended to limit the environment, favouring further muscle damage.

Rheumatology Article