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02 July 2004

cDNA microarrays reveal distinct gene expression clusters in idiopathic inflammatory myopathies

Xiaodong Zhou, Mazen M. Dimachkie, Momiao Xiong, Filemon K. Tan, Frank C. Arnett

Med Sci Monit 2004; 10(7): BR191-197 :: ID: 11712

Abstract

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.Material/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.

Keywords: Biopsy, Case-Control Studies, Cluster Analysis, Creatine Kinase - metabolism, Dermatomyositis - genetics, Dermatomyositis - immunology, Dermatomyositis - metabolism, Dermatomyositis - pathology, Electromyography, Multigene Family, Muscle, Skeletal - pathology, Oligonucleotide Array Sequence Analysis, Polymyositis - genetics, Polymyositis - immunology, Polymyositis - metabolism, Polymyositis - pathology, Biopsy, Case-Control Studies, Cluster Analysis, Creatine Kinase - metabolism, Dermatomyositis - pathology, Electromyography, Multigene Family, Muscle, Skeletal - pathology, Oligonucleotide Array Sequence Analysis, Polymyositis - pathology

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750