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SAT0004 Genomic signatures characterize leukocyte infiltration in myositis muscles
  1. W. Zhu1,
  2. K. Streicher1,
  3. N. Shen2,
  4. B.W. Higgs1,
  5. C. Morehouse1,
  6. L. Greenlees1,
  7. K. Ranade1,
  8. L. Richman1,
  9. D. Fiorentino3,
  10. B. Jallal4,
  11. S.A. Greenberg5,
  12. Y. Yao1
  1. 1Translational Sciences, MedImmune, Gaithersburg, United States
  2. 2Shanghai Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
  3. 3Department of Dermatology, Stanford University School of Medicine, Stanford
  4. 4Research, MedImmune, Gaithersburg
  5. 5Department of Neurology, Brigham and Women’s Hospital, Harvard Medical School, Boston, United States

Abstract

Background Leukocyte infiltration plays an important role in the pathogenesis and progression of myositis, and is highly associated with disease severity.

Objectives We employed a genomics approach to assess the inflammatory cell infiltration in myositis.

Methods Muscle biopsies from 31 myositis patients and 5 normal healthy donors were profiled by microarray in parallel with microRNA (miRNA) expression analyses.

Results Several gene signatures, such as the leukocyte index, type 1 interferon (IFN), MHC-1 and immunoglobulin signatures, were developed to characterize myositis patients at the molecular level. The leukocyte index was comprised of genes predominantly associated with the immune function and displayed a strong concordance with the pathological assessment of immune cell infiltration. This leukocyte index was subsequently utilized to evaluate expression changes of transcripts due to leukocyte infiltration in myositis muscle biopsies. The ability to distinguish different sources of altered gene expression in heterogeneous tissues increased our understanding of the complex interactions crucial to the pathogenesis of myositis. Such approach can be applied to various other studies and allowed more accurate interpretation of the underlying biology with gene expression data from heterogenous tissue samples. One application of the leukocyte index comparing miRNA and mRNA expression profiles revealed a complex interaction between miR-146a expression and the regulation of the type 1 IFN pathway in dermatomyositis.

Conclusions Collectively, the distinct miRNA and mRNA signatures identified in this study may contribute to the development of new therapeutic targets and provide utility as molecular biomarkers for characterizing inflammatory myopathies.

Disclosure of Interest W. Zhu Shareholder of: Astra Zeneca, Employee of: MedImmune, K. Streicher Shareholder of: Astra Zeneca, Employee of: MedImmune, N. Shen Consultant for: MedImmune, B. Higgs Shareholder of: Astra Zeneca, Employee of: MedImmune, C. Morehouse Shareholder of: Astra Zeneca, Employee of: MedImmune, L. Greenlees Shareholder of: Astra Zeneca, Employee of: MedImmune, K. Ranade Shareholder of: Astra Zeneca, Employee of: MedImmune, L. Richman Shareholder of: Astra Zeneca, Employee of: MedImmune, D. Fiorentino: None Declared, B. Jallal Shareholder of: Astra Zeneca, Employee of: MedImmune, S. Greenberg Consultant for: MedImmune, Y. Yao Shareholder of: Astra Zeneca, Employee of: MedImmune

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