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13 November 2013 : Original article  

Influence of the immunogenetic KIR and HLA systems on long-term renal transplant outcome

Gaetano La MannaACDEFG, Serena CorsiniBCDF, Sandra IannelliABDF, Maria Laura CappuccilliACDEF, Giorgia ComaiBCD, Mario IorioBC, Paola TodeschiniADF, Elisa CarrettaCD, Maria Piera ScolariADF, Andrea BontadiniACDFG, Segio StefoniAFG

DOI: 10.12659/AOT.889157

Ann Transplant 2013; 18:611-621

Abstract

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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Annals of Transplantation eISSN: 2329-0358
Annals of Transplantation eISSN: 2329-0358