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



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.



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.



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.
Karolinska Institutet, Department of Medicine, Rheumatology Unit, Karolinska University Hospital Solna, Stockholm, Sweden.
Ingela
I
Loell
Karolinska Institutet, Department of Medicine, Rheumatology Unit, Karolinska University Hospital Solna, Stockholm, Sweden.
Joan
J
Raouf
Childrens National Medical Center, Research Center for Genetic Medicine, Washington, DC, USA.
Yi-Wen
YW
Chen
Center for Human Immunology, Autoimmunity and Inflammation, National Heart/Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
Rongye
R
Shi
Karolinska University Hospital Huddinge, Institution for Laboratory Medicine (LABMED), Stockholm, Sweden.
Inger
I
Nennesmo
Karolinska Institutet, Department of NVS, Division of Physical Therapy and Karolinska University Hospital Solna, Physical Therapy Clinic, Stockholm, Sweden.
Helene
H
Alexanderson
Karolinska Institutet, Department of Medicine, Rheumatology Unit, Karolinska University Hospital Solna, Stockholm, Sweden.
Maryam
M
Dastmalchi
Childrens National Medical Center, Research Center for Genetic Medicine, Washington, DC, USA.
Kanneboyina
K
Nagaraju
Karolinska Institutet, Department of Medicine, Rheumatology Unit, Karolinska University Hospital Solna, Stockholm, Sweden.
Marina
M
Korotkova
Karolinska Institutet, Department of Medicine, Rheumatology Unit, Karolinska University Hospital Solna, Stockholm, Sweden. Ingrid.Lundberg@ki.se.
Ingrid E
IE
Lundberg
D000328:Adult; D000368:Aged; D001706:Biopsy; D015153:Blotting, Western; D003882:Dermatomyositis / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D050356:Lipid Metabolism / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D017285:Polymyositis / Q000188:drug therapy* / Q000378:metabolism; D059467:Transcriptome / Q000187:drug effects
D007166:Immunosuppressive Agents
Dermatomyositis; Gene expression profiling; Glucocorticoids; Muscle biopsies; Polymyositis; Treatment