13 November 2013 : Original article
Influence of the immunogenetic KIR and HLA systems on long-term renal transplant outcomeGaetano La MannaACDEFG, Serena CorsiniBCDF, Sandra IannelliABDF, Maria Laura CappuccilliACDEF, Giorgia ComaiBCD, Mario IorioBC, Paola TodeschiniADF, Elisa CarrettaCD, Maria Piera ScolariADF, Andrea BontadiniACDFG, Segio StefoniAFG
Ann Transplant 2013; 18:611-621
BACKGROUND: Numerous studies have established the importance of innate immunity, particularly natural killer (NK) cells, in transplantation tolerance. NK cells express killer cell immunoglobulin-like receptors (KIRs) on their surface. By recognizing and binding major histocompatibility complex class I antigens, KIRs prevent autologous cell killing and promote lysis of non-self antigen-presenting cells. This study investigated the role of 16 KIR genes and donor-recipient KIR/HLA combinations on 5-year outcomes in a population of deceased donor kidney transplant recipients.
MATERIAL AND METHODS: We genotyped 126 renal transplant patients and their donors for HLA A, B, C, DR, and KIR genes. Patients underwent standardized transplantation and immunosuppressive protocols and were followed-up for 5 years. Graft function was evaluated by serum creatinine level and glomerular filtration rate calculated using the 4-variable modification of diet in renal disease (MDRD) equation.
RESULTS: The presence of KIR2DS3 in the recipients was associated with better graft function indexes over time (p<0.05), but this effect was not confirmed by multivariate analysis. Conversely, the presence KIR2DS3 in the recipients combined with the presence of its HLA ligand in the donor had a detrimental effect on the trends of serum creatinine levels and eGFR trends, also confirmed by multivariate analysis. Kidney transplant recipients negative for the KIR2DL1 gene displayed higher creatinine levels after 5 years. Lastly, transplantation of HLA-A3/A11-negative donor kidneys into KIR3DL2-positive patients exerted a protective effect in terms of 5-years outcome (p<0.05).
CONCLUSIONS: The present study demonstrates an important role of the KIR immunogenetic system in the long-term immune response to kidney transplantation.
Keywords: Killer cell immunoglobulin-like receptor, KIR, Kidney Transplantation, Human leukocyte antigen, HLA, Long-term transplant outcome, Natural killer cells, NK, receptor – KIR
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