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INCOMPATIBILITY BETWEEN KIR2DL1 AND ITS HLA-C LIGANDS IS ASSOCIATED WITH ACUTE REJECTION IN KIDNEY TRANSPLANTATION.
Marleen Seiler 1, Constanze Schoenemann PhD 2, Mir Farzin Mashreghi 1, 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 of Transfusion Medicine, Universitaetsmedizin Charité, Berlin, Germany and 3 Department of Nephrology and Intensive Care, Universitaetsmedizin Charité, Berlin, Germany .
The polymorphic killer-cell-immunoglobulin-like receptors (KIRs) are expressed by NK cells and subsets of T cells. It has been shown that KIR/HLA incompatibility exerts beneficial effects in bone marrow transplantation. Despite the knowledge about recipient NK-cell cytotoxicity against the graft in renal transplantation, little is known about the functional role of KIR/Ligand incompatibility in this transplant setting.
We designed a PCR-SSP for genotyping of 16 KIR genes comprising 18 primer mixes. Genotyping for HLA was performed routinely prior to Tx. In our study group 67/136 patients suffered from biopsy proven acute rejection (aRx) episodes after kidney transplantation.
Data were analyzed for the entirety of matches/mismatches between activating and inhibitory KIR genes and their known HLA ligands. In summary, patients with an uncomplicated course displayed a higher number for KIR/HLA matches compared to the aRx group. This observation was made for inhibitory and activating KIR receptors. Despite this observation the analysis revealed that aRx rejecting patients demonstrated a significant higher number of mismatches between the inhibitory receptor KIR2DL1 and its corresponding HLA-C group 2 alleles (p=0.005). These are the first data illustrating the influence of KIR/HLA incompatibility in renal transplantation suggesting that allografts which do not express recipient MHC class I molecules, can be potential targets for NK-cell killing with consequences for graft outcome.