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A2.6 Cell-Specific Type I IFN Signatures in Autoimmunity and Viral Infection: What Makes the Difference?
  1. Chieko Kyogoku1,
  2. Biljana Smiljanovic1,
  3. Joachim R Grün1,
  4. Tobias Alexander2,
  5. Robert Biesen2,
  6. Falk Hiepe2,
  7. Thomas Häupl2,
  8. Andreas Radbruch1,
  9. Andreas Grützkau1
  1. 1German Rheumatism Research Centre (DRFZ) Berlin, An Institute of the Leibniz Association, Berlin, Germany
  2. 2Department of Rheumatology and Clinical Immunology, Charité University Medicine Berlin, Humboldt University of Berlin, Berlin, Germany

Abstract

Background Gene expression profiling experiments using peripheral blood mononuclear cells (PBMCs) revealed a crucial role of type I interferon (IFN) in the pathogenesis of systemic lupus erythematosus (SLE). However, it is almost unknown how particular leukocyte subsets contribute to the overall type I IFN signature described for PBMCs. Furthermore, a detailed analysis of how IFN signatures differ in autoimmune disease from that observed after viral infection is missing so far. Therefore, we compared expression levels of 2442 IFN signature genes in peripheral CD4+ T helper cells and monocyte (Mo) subsets isolated from patients with SLE, healthy donors (ND) and ND vaccinated against yellow fever by global gene expression profiling.

Materials and Methods Peripheral blood from 8 patients with SLE and 4 ND were recruited. Same ND were examined before and after immunisation by yellow fever vaccine. After sorting cells, isolated RNA were applied to Affymetrix Human Genome U133 Plus 2.0 Array. Data analysis was done using BioRetis database, Genesis Software and Ingenuity Pathway Analysis (IPA).

Results 98/165/173 probe sets (CD4+ T cells/CD16– inflammatory Mo/CD16+ resident Mo, respectively, fold change ≥ 2, ≤ –2) were detected as a “common” IFN signature observed both in autoimmunity and in immunised ND. 111/164/120 probe sets were detected as an “autoimmune-specific” IFN signature, whereas only 0/8/5 probe sets were detected to be specific for the “virus-induced” IFN signature. Expression pattern of these IFN signature genes clearly distinguished patients with SLE from immunised ND by hierarchical cluster analysis. Although major IFN signature genes were commonly expressed in CD4+ T cells and Mo of patients with SLE and immunised ND, expression magnitudes of them were higher in patients with SLE compared to immunised ND. In SLE, in addition to the typical “viral-induced” IFN signature, genes that are involved in apoptosis signalling, antiviral PKR signalling, Fcγ receptor-mediated phagocytosis and IL-10-/IL-9-/IL-15-mediated JAK/Stat signalling pathways were identified by IPA.

Conclusions This study demonstrated that IFN signature in autoimmunity and that in viral infection are quite different in the number of IFN-related genes activated and their expression magnitudes. Autoimmunity is characterised by a much stronger expression of IFN signature genes and is obviously modulated by a separate set of co-regulated genes defining the “autoimmune-specific” IFN signature. “Common” and “autoimmune-specific” IFN signature genes can be applied as a clinical biomarker to diagnose SLE flare discriminating from viral infection.

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