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AB0198 Defining CD4+ T cell- and monocyte-specific interferon signatures in active, inactive and autologous stem cell transplanted lupus patients by global gene expression profiling
  1. C. Kyogoku1,
  2. J. Grün1,
  3. R. Biesen2,
  4. T. Alexander2,
  5. T. Häupl2,
  6. F. Hiepe2,
  7. A. Radbruch1,
  8. A. Grützkau1
  1. 1Leibniz Institute, FCCF, Deutsches Rheuma-Forschungszentrum Berlin (Drfz)
  2. 2Dept. Rheumatology and Clinical Immunology, Charité, Faculty of Humboldt-University, Berlin, Germany

Abstract

Background Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease that affects multiple organs, whose pathology is mainly caused by the augmented interferon (IFN) signaling pathway.

Objectives The objective of this study was to analyze the particular contribution of peripheral T helper lymphocytes and monocytes with respect to cell type-specific IFN signatures detectable in SLE by global gene expression profiling. The major focus was set on the comparison of disease-active and -inactive patients either by standard drug treatment or by autologous stem cell transplantation (ASCT) that is assumed to completely reset the autoreactive immunologic memory (1).

Methods Affymetrix HG U133 Plus 2.0 gene expression arrays were made from purified peripheral CD4+ T cells from three active SLE, two inactive SLE by standard drug treatment and three inactive SLE who underwent ASCT as well as three healthy donors. In addition, using the same donors, arrays were made from purified monocytes from one active SLE, one inactive SLE, three ASCT-treated SLE and three healthy donors. A reference list of 2220 IFN pathway-related genes was obtained from a recent publication on PBMCs (2) and used to estimate IFN imprints in SLE patients.

Results Comparing IFN-imprints of CD4+ T cells in active, inactive and ASCT-treated inactive SLE patients, it was obvious that inactive SLE showed a marginal IFN-imprint characterized by 233 only weakly expressed probe sets compared to active SLE characterized by 573 probe sets. Unexpectedly, 562 differentially expressed probe sets were also identified in ASCT-treated patients who are under long-term remission for several years. However, considering the absolute magnitude of expression of IFN-regulated transcripts, it was obvious that the imprint was much weaker as compared to active SLE, but stronger than in inactive SLE under standard immunosuppressive drug therapy. Comparing CD4+ T cells and monocytes from active SLE, it was obvious that monocytes showed a more complex IFN response characterized by 918 differentially expressed probe sets. Different from CD4+ T cells, monocytes from ASCT-treated patients showed no prominent IFN signatures.

Conclusions We could show for the first time detailed cell type-specific IFN signatures for peripheral T helper lymphocytes and monocytes isolated from active and inactive SLE patients. Most interestingly, the intriguing question comes up, why CD4+ T cells of all ASCT-treated patients investigated in this study are characterized by a prominent IFN imprint although patients are under long-term remission. Our data make it reasonable to assume that CD4+ T cells, but not monocytes from ASCT-treated patients are sensitive biosensors for an activated type I interferon system that may be used diagnostically to predict a future clinical relapse.

  1. Alexander T et al. Blood. 2009 Jan 1;113(1):214-23.

  2. Ramos PS et al. Arthritis Rheum. 2011 Jul;63(7):2049-57.

Disclosure of Interest None Declared

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