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A8.16 T helper lymphocytes and monocytes as biosensors of type I interferon responses in viral infection and autoimmunity
  1. Chieko Kyogoku1,
  2. Biljana Smiljanovic2,
  3. Joachim R Grün1,
  4. Ursula Schulte-Wrede1,
  5. Tobias Alexander2,
  6. Robert Biesen2,
  7. Falk Hiepe2,
  8. Thomas Häupl2,
  9. Andreas Radbruch1,
  10. Andreas Grützkau1
  1. 1German Rheumatism Research Centre (DRFZ) Berlin, An Institute of the Leibniz Association, Berlin, Germany
  2. 2Department of Rheumatology andClinical Immunology, Charité University Medicine Berlin, Humboldt University of Berlin, Berlin, Germany

Abstract

Background Immune responses in viral infections and autoimmunity are characterised by type I interferon (IFN) gene signatures detectable in peripheral blood mononuclear cells (PBMC). We have identified cell-specific IFN signatures in CD4 T cells and in monocyte subsets and could use them to discriminate between physiologic and pathologically sustained type I responses in yellow fever vaccinated individuals and in systemic lupus erythematosus patients (SLE). In this study we show that these cell-specific IFN signatures are not only working in isolated cell subsets but are even robust enough to classify PBMC in viral infection and autoimmunity.

Materials and Methods We have used whole genome expression arrays to identify cell-specific type I IFN response signatures in isolated CD4 lymphocytes, CD16+ and CD16- monocyte subsets. These signatures were used to classify independent PBMC samples of yellow fever vaccinated individuals (n = 10) and jSLE patients (n = 10).

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. Interestingly, these cell-specifically generated expression signatures were successfully used to classify PBMC of viral infection and jSLE by hierarchical cluster analyses.

Conclusion 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. These cell-specific signatures are robust enough to classify PBMC samples. In summary, “common” and “autoimmune-specific” IFN signature genes are of potential interest as clinical biomarkers in SLE diagnostics to differentiate between a disease flare and a viral infection.

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