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


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.
Section of Nephrology and Renal Transplant, Department of Specialistic, Diagnostic and Experimental Medicine, University of Bologna, Bologna, Italy.
Gaetano
G
La Manna
Serena
S
Corsini
Sandra
S
Iannelli
Maria Laura
ML
Cappuccilli
Giorgia
G
Comai
Mario
M
Iorio
Paola
P
Todeschini
Elisa
E
Carretta
Maria Piera
MP
Scolari
Andrea
A
Bontadini
Segio
S
Stefoni
D000328:Adult; D000368:Aged; D005260:Female; D005838:Genotype; D006085:Graft Survival / Q000276:immunology*; D006680:HLA Antigens / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D054340:Receptors, KIR / Q000235:genetics* / Q000378:metabolism
D006680:HLA Antigens; D007166:Immunosuppressive Agents; D054340:Receptors, KIR