TY - JOUR
T1 - Interleukin-6 and type I interferon-regulated genes and chemokines Mark disease activity in dermatomyositis
AU - Bilgic, Hatice
AU - Ytterberg, Steven R.
AU - Amin, Shreyasee
AU - McNallan, Kelly T.
AU - Wilson, Joseph C.
AU - Koeuth, Thearith
AU - Ellingson, Sonja
AU - Newman, Brant
AU - Bauer, Jason W.
AU - Peterson, Erik J.
AU - Baechler, Emily C.
AU - Reed, Ann M.
PY - 2009/11
Y1 - 2009/11
N2 - 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 α chemoattractant, IFNγ-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. Conclusion. 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 IFNdriven chemokines and IL-6 suggests a novel pathogenic linkage in DM.
AB - 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 α chemoattractant, IFNγ-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. Conclusion. 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 IFNdriven chemokines and IL-6 suggests a novel pathogenic linkage in DM.
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U2 - 10.1002/art.24936
DO - 10.1002/art.24936
M3 - Article
C2 - 19877033
AN - SCOPUS:70350523961
VL - 60
SP - 3436
EP - 3446
JO - Arthritis and Rheumatology
JF - Arthritis and Rheumatology
SN - 2326-5191
IS - 11
ER -