Effects on muscle tissue remodeling and lipid metabolism in muscle tissue from adult patients with polymyositis or dermatomyositis treated with immunosuppressive agents

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Abstract

Background

Polymyositis (PM) and dermatomyositis (DM) are autoimmune muscle diseases, conventionally treated with high doses of glucocorticoids in combination with immunosuppressive drugs. Treatment is often dissatisfying, with persisting muscle impairment. We aimed to investigate molecular mechanisms that might contribute to the persisting muscle impairment despite immunosuppressive treatment in adult patients with PM or DM using gene expression profiling of repeated muscle biopsies.

Methods

Paired skeletal muscle biopsies from six newly diagnosed adult patients with DM or PM taken before and after conventional immunosuppressive treatment were examined by gene expression microarray analysis. Selected genes that displayed changes in expression were analyzed by Western blot. Muscle biopsy sections were evaluated for inflammation, T lymphocytes (CD3), macrophages (CD68), major histocompatibility complex (MHC) class I expression and fiber type composition.

Results

After treatment, genes related to immune response and inflammation, including inflammasome pathways and interferon, were downregulated. This was confirmed at the protein level for AIM-2 and caspase-1 in the inflammasome pathway. Changes in genes involved in muscle tissue remodeling suggested a negative effect on muscle regeneration and growth. Gene markers for fast type II fibers were upregulated and fiber composition was switched towards type II fibers in response to treatment. The expression of genes involved in lipid metabolism was altered, suggesting a potential lipotoxic effect on muscles of the immunosuppressive treatment.

Conclusion

The anti-inflammatory effect of immunosuppressive treatment was combined with negative effects on genes involved in muscle tissue remodeling and lipid metabolism, suggesting a negative effect on recovery of muscle performance which may contribute to persisting muscle impairment in adult patients with DM and PM.

Related collections

Most cited references 27

Record: found
Abstract: found
Article: not found

Lipotoxicity: when tissues overeat

Jean E. Schaffer (2003)

This review will provide the reader with an update on our understanding of the adverse effects of fatty acid accumulation in non-adipose tissues, a phenomenon known as lipotoxicity. Recent studies will be reviewed. Cellular mechanisms involved in the lipotoxic response will be discussed. Physiologic responses to lipid overload and therapeutic approaches to decreasing lipid accumulation will be discussed, as they add to our understanding of important pathophysiologic mechanisms.

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Record: found
Abstract: not found
Article: not found

Three "myosin adenosine triphosphatase" systems: the nature of their pH lability and sulfhydryl dependence.

Mary K. Kaiser, H Brooke (1970)

0 comments Cited 126 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

The RIG-I-like receptor IFIH1/MDA5 is a dermatomyositis-specific autoantigen identified by the anti-CADM-140 antibody.

Daisuke Kawabata, Tsuneyo Mimori, Hajime Yoshifuji … (2010)

Various autoantibodies are detected in the sera of PM/DM patients. Some of them are specific to PM/DM patients and closely associated with clinical manifestations of the diseases. Recently, the anti-CADM-140 antibody was reported to be found specifically in clinically amyopathic DM (C-ADM) patients and to be associated with acute interstitial lung disease (ILD). We assessed the clinical significance of the anti-CADM-140 antibody and then investigated the autoantigen recognized by the anti-CADM-140 antibody. Autoantibodies were screened in 192 patients with various CTDs and 21 healthy controls using immunoprecipitation with [(35)S]methionine-labelled HeLa cells. Immunoabsorbent column chromatography was used to purify an autoantigen that was subsequently subjected to peptide mass fingerprinting. The anti-CADM-140 antibody was revealed to be specific to DM. Most of the anti-CADM-140-positive patients were C-ADM although some of them showed apparent myositis. The anti-CADM-140-positive patients frequently showed hyperferritinaemia and acute progressive ILD with poor prognosis. The anti-CADM-140 antibody was shown to recognize IFN induced with helicase C domain protein 1 (IFIH1), also known as the melanoma differentiation-associated gene 5 (MDA5), which is one of the RIG-I-like receptors and plays a role in innate immune responses. The anti-CADM-140 antibody was a marker of DM and intractable ILD and recognized IFIH1/MDA5, which is involved in innate immunity. These findings may give a new insight into the pathogenesis of DM.

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Author and article information

Contributors

Ingrid E. Lundberg: (46) 8 51776 087 , (46) 8 5173080 , Ingrid.Lundberg@ki.se

Journal

Journal ID (nlm-ta): Arthritis Res Ther

Journal ID (iso-abbrev): Arthritis Res. Ther

Title: Arthritis Research & Therapy

Publisher: BioMed Central (London )

ISSN (Print): 1478-6354

ISSN (Electronic): 1478-6362

Publication date (Electronic): 10 June 2016

Publication date PMC-release: 10 June 2016

Publication date (Print): 2016

Volume: 18

Electronic Location Identifier: 136

Affiliations

[ ]Karolinska Institutet, Department of Medicine, Rheumatology Unit, Karolinska University Hospital Solna, Stockholm, Sweden

[ ]Childrens National Medical Center, Research Center for Genetic Medicine, Washington, DC USA

[ ]Center for Human Immunology, Autoimmunity and Inflammation, National Heart/Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland USA

[ ]Karolinska University Hospital Huddinge, Institution for Laboratory Medicine (LABMED), Stockholm, Sweden

[ ]Karolinska Institutet, Department of NVS, Division of Physical Therapy and Karolinska University Hospital Solna, Physical Therapy Clinic, Stockholm, Sweden

Article

Publisher ID: 1033

DOI: 10.1186/s13075-016-1033-y

PMC ID: 4902919

PubMed ID: 27287443

SO-VID: 699b9669-01a4-4375-bb20-d8f7db6faa5a

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 8 October 2015

Date accepted : 25 May 2016