Type I interferon-inducible gene expression in blood is present and reflects disease activity in dermatomyositis and polymyositis.
OBJECTIVE
To apply gene expression profiling to the study of peripheral blood mononuclear cells from patients with inflammatory myopathies, in order to provide insight into disease pathogenesis and identify potential biomarkers associated with disease activity.


METHODS
We used Affymetrix whole-genome microarrays to measure the expression of approximately 38,500 genes in 65 blood and 15 muscle samples from 44 patients with dermatomyositis (DM), polymyositis (PM), inclusion body myositis (IBM), myasthenia gravis, or genetically determined myopathies and from 12 healthy volunteers. In 9 patients, 2 samples were obtained at different time points, when disease was either active or improving, and these paired blood samples were also compared. Bioinformatics techniques were used to identify genes with significant differential expression among diagnostic categories and in relation to disease activity. We corroborated the microarray data with quantitative real-time reverse transcriptase-polymerase chain reaction.


RESULTS
Most patients with active DM or PM, but not patients with IBM, had significant and high up-regulation of the type I interferon-alpha/beta (IFNalpha/beta)-inducible genes in blood. Furthermore, the up-regulation of these genes correlated with disease activity in DM and PM, with down-regulation occurring when disease was controlled with treatment.


CONCLUSIONS
DM and PM are diseases characterized by the systemic overexpression of IFNalpha/beta-inducible genes. The magnitude of the overexpression of these genes is higher in DM and correlates with disease activity in both disorders. Although PM and IBM have been modeled as having similar immunologic processes occurring within muscle, there are substantial differences in the expression of IFNalpha/beta-inducible genes in blood in these diseases.
Walsh
Ronan J
RJ
Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Kong
Sek Won
SW
Yao
Yihong
Y
Jallal
Bahija
B
Kiener
Peter A
PA
Pinkus
Jack L
JL
Beggs
Alan H
AH
Amato
Anthony A
AA
Greenberg
Steven A
SA
D000328:Adult; D000368:Aged; D003882:Dermatomyositis / Q000235:genetics*; D015536:Down-Regulation; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics; D020869:Gene Expression Profiling; D006801:Humans; D016898:Interferon-alpha / Q000235:genetics*; D016899:Interferon-beta / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000502:physiology; D064547:Myxovirus Resistance Proteins; D020411:Oligonucleotide Array Sequence Analysis; D017285:Polymyositis / Q000235:genetics*; D012333:RNA, Messenger / Q000097:blood; D015854:Up-Regulation
D016898:Interferon-alpha; D064547:Myxovirus Resistance Proteins; D012333:RNA, Messenger; D016899:Interferon-beta; D019204:GTP-Binding Proteins