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MRNA INDUCTION OF THE NK CELL RECEPTOR NKG2D DURING ACUTE REJECTION FOLLOWING KIDNEY TRANSPLANATION.
Marleen Seiler 1, Irena Brabcova 2, Jiri Lacha MD 2, Petra Reinke MD 3, Hans-Dieter Volk MD 1 and Katja Kotsch PhD 1. 1 Institute of Medical Immunology, Universitaetsmedizin Charité, Berlin, Germany ; 2 Institute for Clinical and Experimental Medicine, Transplant Laboratory, Prague, Czech Republic and 3 Department of Nephrology and Intensive Care, Universitaetsmedizin Charité, Berlin, Germany .
Intention: NKG2D is an activating natural cytotoxicity receptor (NCR) which binds to MHC class I chain-related (MICA) antigens. The stress-inducible MICA molecules have been shown to be expressed on e.g. epithelial, endothelial cells and activated CD4+/CD8+ T cells. Acute rejection (aRx) following renal transplantation implicates cellular stress within the graft. To assess whether an induction of MICA antigen leads to enhanced activation of NKG2D during aRx, we examined mRNA profiles of both markers in biopsies and urine sediment during aRx. Material and Methods: Using RT-PCR 31 biopsy samples diagnosed as aRx were investigated for MICA and NKG2D mRNA expression and were compared to control biopsies (n=32). In a second patient group 188 urine samples were collected from renal-allograft rejecting recipients (n=55) during aRx and compared to 43 patients with stable renal function (n=84). Results: The analysis revealed a significant mRNA upregulation of NKG2D (p<0.001) in biopsies diagnosed as aRx compared to the controls. ROC curve analysis for NKG2D demonstrated a sensitivity and specificity of 65% and 91%. Highly mRNA induction particularly for the NK cell receptor NKG2D (p<0.01) was uncovered in urine sediment in patients with aRx. However, no significant mRNA induction for MICA was observed for biopsy and urine specimens. Conclusion: Our data describe the significant mRNA expression of NKG2D during renal aRx suggesting the triggering of innate NK cell responses during renal allograft aRx.