Interleukin-6 and type I interferon-regulated genes and chemokines mark disease activity in dermatomyositis

Arthritis Rheum. 2009 Nov;60(11):3436-46. doi: 10.1002/art.24936.

Abstract

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.

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 IFN-driven chemokines and IL-6 suggests a novel pathogenic linkage in DM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers / blood
  • Carrier Proteins / blood
  • Case-Control Studies
  • Chemokine CCL2 / blood
  • Chemokine CCL8 / blood
  • Chemokine CXCL10 / blood
  • Chemokine CXCL11 / blood
  • Chemokines / blood*
  • Child
  • Cytokines / blood
  • Dermatomyositis / blood*
  • Dermatomyositis / diagnosis
  • Female
  • Humans
  • Interferon Regulatory Factor-7 / blood
  • Interferon Type I / genetics*
  • Interleukin-6 / blood*
  • Male
  • Middle Aged
  • Severity of Illness Index*
  • Ubiquitins / blood
  • Young Adult

Substances

  • Biomarkers
  • CCL2 protein, human
  • CCL8 protein, human
  • CXCL10 protein, human
  • CXCL11 protein, human
  • Carrier Proteins
  • Chemokine CCL2
  • Chemokine CCL8
  • Chemokine CXCL10
  • Chemokine CXCL11
  • Chemokines
  • Cytokines
  • IFIT1 protein, human
  • IRF7 protein, human
  • Interferon Regulatory Factor-7
  • Interferon Type I
  • Interleukin-6
  • Ubiquitins
  • ISG15 protein, human