cDNA microarrays reveal distinct gene expression clusters in idiopathic inflammatory myopathies.
BACKGROUND
Polymyositis (PM) and dermatomyositis (DM) are complex human diseases of autoimmune origin which cause progressive skeletal muscle weakness in adults and children. Histopathological studies of affected muscles suggest that cytotoxic T cell-induced injury predominates in PM, while humoral immune mechanisms seem more likely in DM. Early expression of MHC class I molecules on myocytes is a striking feature of both disorders. This study was to use gene microarray analysis of muscle biopsies from PM and DM patients to obtain a comprehensive view of molecules participating in disease pathogenesis.


METHODS
Muscle biopsies from 10 patients (6 PM and 4 DM) and 5 controls were selected for gene expression profiles. Microarray filters containing 4000 known human genes were used to hybridize with RNAs from muscle biopsies. Real-time RT-PCR assays were used to confirmed selected genes that showed changes in expression levels in PM and DM from microarray data. The t-statistic was used to measure any differences in the amount of gene expression in the normal versus myositis biopsies.


RESULTS
Forty genes clustering into two major groups showed significantly altered expression levels in PM/DM compared to normal biopsies. One cluster of over-expressed genes was primarily of immune origin and included HLA-class I and II, interferon-inducible proteins, natural killer (NK) protein, immunoglobulins and complement. The other cluster of under-expressed genes were of muscle origin, especially those involved in the fast twitch response. PM and DM gene profiles appeared similar.


CONCLUSIONS
PM and DM muscle biopsies show similar gene expression profiles despite reported differences in histopathological changes. Altered gene expressions of immune regulation and myofibrillar proteins are prominent in muscle biopsies of myositis.
Zhou
Xiaodong
X
Division of Rheumatology and Clinical Immunogenetics, Department of Internal Medicine, the University of Texas Medical School at Houston, Houston, TX 77030, USA. xiaodong.zhou@uth.tmc.edu
Dimachkie
Mazen M
MM
Xiong
Momiao
M
Tan
Filemon K
FK
Arnett
Frank C
FC
D000328:Adult; D000368:Aged; D001706:Biopsy; D016022:Case-Control Studies; D016000:Cluster Analysis; D003402:Creatine Kinase / Q000378:metabolism; D003882:Dermatomyositis / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004576:Electromyography; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D005810:Multigene Family; D018482:Muscle, Skeletal / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D017285:Polymyositis / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000473:pathology
D003402:Creatine Kinase