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.

Department of Pathology and Molecular Medicine 2nd Medical School and University Hospital Motol Charles University Prague Czech Republic

Institute of Experimental Endocrinology Biomedical Research Center Slovak Academy of Sciences Bratislava and Institute of Pathophysiology Faculty of Medicine Comenius University Bratislava Slovakia

Institute of Experimental Endocrinology Biomedical Research Center Slovak Academy of Sciences Bratislava Slovakia

Institute of Rheumatology Prague and Department of Physiotherapy Faculty of Physical Education and Sport Charles University Prague Czech Republic

Institute of Rheumatology Prague and Department of Rheumatology 1st Faculty of Medicine Charles University Prague Czech Republic

Institute of Rheumatology Prague and Faculty of Science Charles University Prague Czech Republic

Institute of Rheumatology Prague Czech Republic

Institute of Rheumatology Prague Czech Republic 4 Department of Physiotherapy Faculty of Physical Education and Sport Charles University Prague Czech Republic

Citace poskytuje Crossref.org

S100A4-neutralizing monoclonal antibody 6B12 counteracts the established experimental skin fibrosis induced by bleomycin

The therapeutic and prognostic role of clusterin in diverse musculoskeletal diseases: a mini review

Inhibition of Hsp90 Counteracts the Established Experimental Dermal Fibrosis Induced by Bleomycin