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Open Access 01-12-2016 | Research article

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

Authors: Ingela Loell, Joan Raouf, Yi-Wen Chen, Rongye Shi, Inger Nennesmo, Helene Alexanderson, Maryam Dastmalchi, Kanneboyina Nagaraju, Marina Korotkova, Ingrid E. Lundberg

Published in: Arthritis Research & Therapy | Issue 1/2016

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.

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Title: Effects on muscle tissue remodeling and lipid metabolism in muscle tissue from adult patients with polymyositis or dermatomyositis treated with immunosuppressive agents
Authors: Ingela Loell
Joan Raouf
Yi-Wen Chen
Rongye Shi
Inger Nennesmo
Helene Alexanderson
Maryam Dastmalchi
Kanneboyina Nagaraju
Marina Korotkova
Ingrid E. Lundberg
Publication date: 01-12-2016
Publisher: BioMed Central
Published in: Arthritis Research & Therapy / Issue 1/2016
Electronic ISSN: 1478-6362
DOI: https://doi.org/10.1186/s13075-016-1033-y

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

Abstract

Background

Methods

Results

Conclusion

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