Interleukin-6 and type I interferon-regulated genes and chemokines mark disease activity in dermatomyositis.
OBJECTIVE
Up-regulation of whole blood type I interferon (IFN)-driven transcripts and chemokines has been described in a number of autoimmune diseases. An IFN gene expression "signature" is a candidate biomarker in patients with dermatomyositis (DM). This study was performed to evaluate the capacity of IFN-dependent peripheral blood gene and chemokine signatures and levels of proinflammatory cytokines to serve as biomarkers for disease activity in adult and juvenile DM.


METHODS
Peripheral blood samples and clinical data were obtained from 56 patients with adult or juvenile DM. The type I IFN gene signature in the whole blood of patients with DM was defined by determining the expression levels of 3 IFN-regulated genes (IFIT1, G1P2, and IRF7) using quantitative real-time reverse transcription-polymerase chain reaction. Multiplexed immunoassays were used to quantify the serum levels of 4 type I IFN-regulated chemokines (IFN-inducible T cell alpha chemoattractant, IFNgamma-inducible 10-kd protein, monocyte chemotactic protein 1 [MCP-1], and MCP-2) and the serum levels of other proinflammatory cytokines, including interleukin-6 (IL-6).


RESULTS
DM disease activity correlated significantly with the type I IFN gene signature (r = 0.41, P = 0.007) and with the type I IFN chemokine signature (r = 0.61, P < 0.0001). Furthermore, the serum levels of IL-6 were significantly correlated with disease activity (r = 0.45, P = 0.001). In addition, correlations between the serum levels of IL-6 and both the type I IFN gene signature (r = 0.47, P < 0.01) and the type I IFN chemokine signature (r = 0.71, P < 0.0001) were detected in patients with DM.


CONCLUSIONS
These results suggest that serum IL-6 production and the type I IFN gene signature are candidate biomarkers for disease activity in adult and juvenile DM. Coregulation of the expression of IFN-driven chemokines and IL-6 suggests a novel pathogenic linkage in DM.
Bilgic
Hatice
H
University of Minnesota, Minneapolis, MN 55455, USA.
Ytterberg
Steven R
SR
Amin
Shreyasee
S
McNallan
Kelly T
KT
Wilson
Joseph C
JC
Koeuth
Thearith
T
Ellingson
Sonja
S
Newman
Brant
B
Bauer
Jason W
JW
Peterson
Erik J
EJ
Baechler
Emily C
EC
Reed
Ann M
AM
D048868:Adaptor Proteins, Signal Transducing; D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002352:Carrier Proteins / Q000097:blood; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000097:blood; D054412:Chemokine CCL8 / Q000097:blood; D054357:Chemokine CXCL10 / Q000097:blood; D054371:Chemokine CXCL11 / Q000097:blood; D018925:Chemokines / Q000097:blood*; D002648:Child; D016207:Cytokines / Q000097:blood; D003882:Dermatomyositis / Q000097:blood* / Q000175:diagnosis; D005260:Female; D006801:Humans; D050839:Interferon Regulatory Factor-7 / Q000097:blood; D007370:Interferon Type I / Q000235:genetics*; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D016601:RNA-Binding Proteins; D012720:Severity of Illness Index; D014452:Ubiquitins / Q000097:blood; D055815:Young Adult
D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; C111835:CCL2 protein, human; C515453:CCL8 protein, human; C114753:CXCL10 protein, human; C515202:CXCL11 protein, human; D002352:Carrier Proteins; D018932:Chemokine CCL2; D054412:Chemokine CCL8; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D018925:Chemokines; D016207:Cytokines; C484290:IFIT1 protein, human; C494234:IRF7 protein, human; D050839:Interferon Regulatory Factor-7; D007370:Interferon Type I; D015850:Interleukin-6; D016601:RNA-Binding Proteins; D014452:Ubiquitins; C074034:ISG15 protein, human