KIR gene and KIR ligand analysis to predict graft rejection after renal transplantation.
BACKGROUND
The identification of transplant patients at high risk for rejection after reduction of immunosuppression would allow minimization of immunosuppression and avoidance of side effects in low-risk patients. Next to T cells, innate natural killer (NK) cells may contribute to graft rejection. NK cell activation depends on the balance between activating and inhibitory signals, delivered by self-human leukocyte antigens (HLA) through binding of killer-cell immunoglobulin receptors (KIR). In transplantation, KIR and/or HLA mismatching may lead to NK cell activation.


METHODS
In this study, we have evaluated whether acute rejection after reduction of immunosuppression after renal transplantation was associated with peripheral blood NK cell frequencies or with predicted NK cell alloreactivity based on KIR gene and ligand analysis. HLA and KIR genotyping was used to analyze the presence of single KIR genes and haplotypes, and to predict NK cell alloreactivity based on the "missing self" and "missing ligand" hypothesis. NK cell frequencies were analyzed using flow cytometry.


RESULTS
No association was found between NK cell alloreactivity based on KIR gene analysis or peripheral blood NK cell subset frequencies and the occurrence of acute rejection after reduction of immunosuppression.


CONCLUSIONS
Our data suggest that in a setting where immunosuppression is reduced, prior analysis of NK cell reactivity cannot identify patients at risk for subsequent graft rejection.
Kreijveld
Ellen
E
Department of Blood Transfusion and Transplantation Immunology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands.
van der Meer
Arnold
A
Tijssen
Henk J
HJ
Hilbrands
Luuk B
LB
Joosten
Irma
I
D000328:Adult; D000939:Epitopes / Q000032:analysis; D005260:Female; D006084:Graft Rejection / Q000453:epidemiology* / Q000235:genetics / Q000517:prevention & control*; D006680:HLA Antigens / Q000032:analysis; D006239:Haplotypes; D006801:Humans; D007165:Immunosuppression Therapy; D015994:Incidence; D007668:Kidney / Q000276:immunology; D016030:Kidney Transplantation; D007694:Killer Cells, Natural / Q000276:immunology*; D008024:Ligands; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D054340:Receptors, KIR / Q000235:genetics*
D000939:Epitopes; D006680:HLA Antigens; D008024:Ligands; D054340:Receptors, KIR