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

Publication ,  Journal Article
Bilgic, H; Ytterberg, SR; Amin, S; McNallan, KT; Wilson, JC; Koeuth, T; Ellingson, S; Newman, B; Bauer, JW; Peterson, EJ; Baechler, EC; Reed, AM
Published in: Arthritis Rheum
November 2009

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.

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Published In

Arthritis Rheum

DOI

ISSN

0004-3591

Publication Date

November 2009

Volume

60

Issue

11

Start / End Page

3436 / 3446

Location

United States

Related Subject Headings

  • Young Adult
  • Ubiquitins
  • Severity of Illness Index
  • RNA-Binding Proteins
  • Middle Aged
  • Male
  • Interleukin-6
  • Interferon Type I
  • Interferon Regulatory Factor-7
  • Humans
 

Citation

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Bilgic, H., Ytterberg, S. R., Amin, S., McNallan, K. T., Wilson, J. C., Koeuth, T., … Reed, A. M. (2009). Interleukin-6 and type I interferon-regulated genes and chemokines mark disease activity in dermatomyositis. Arthritis Rheum, 60(11), 3436–3446. https://doi.org/10.1002/art.24936
Bilgic, Hatice, Steven R. Ytterberg, Shreyasee Amin, Kelly T. McNallan, Joseph C. Wilson, Thearith Koeuth, Sonja Ellingson, et al. “Interleukin-6 and type I interferon-regulated genes and chemokines mark disease activity in dermatomyositis.Arthritis Rheum 60, no. 11 (November 2009): 3436–46. https://doi.org/10.1002/art.24936.
Bilgic H, Ytterberg SR, Amin S, McNallan KT, Wilson JC, Koeuth T, et al. Interleukin-6 and type I interferon-regulated genes and chemokines mark disease activity in dermatomyositis. Arthritis Rheum. 2009 Nov;60(11):3436–46.
Bilgic, Hatice, et al. “Interleukin-6 and type I interferon-regulated genes and chemokines mark disease activity in dermatomyositis.Arthritis Rheum, vol. 60, no. 11, Nov. 2009, pp. 3436–46. Pubmed, doi:10.1002/art.24936.
Bilgic H, Ytterberg SR, Amin S, McNallan KT, Wilson JC, Koeuth T, Ellingson S, Newman B, Bauer JW, Peterson EJ, Baechler EC, Reed AM. Interleukin-6 and type I interferon-regulated genes and chemokines mark disease activity in dermatomyositis. Arthritis Rheum. 2009 Nov;60(11):3436–3446.
Journal cover image

Published In

Arthritis Rheum

DOI

ISSN

0004-3591

Publication Date

November 2009

Volume

60

Issue

11

Start / End Page

3436 / 3446

Location

United States

Related Subject Headings

  • Young Adult
  • Ubiquitins
  • Severity of Illness Index
  • RNA-Binding Proteins
  • Middle Aged
  • Male
  • Interleukin-6
  • Interferon Type I
  • Interferon Regulatory Factor-7
  • Humans