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http://purl.uniprot.org/citations/28686681http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/28686681http://www.w3.org/2000/01/rdf-schema#comment"

Background

Kidney transplantation is a life-saving treatment for patients with end-stage renal disease. However, despite progress in surgical techniques and patient management, immunological rejection continues to have a negative impact on graft function and overall survival. Incompatibility between donors and recipients for human leukocyte antigens (HLA) of the major histocompatibility complex (MHC) generates a series of complex cellular and humoral immune response mechanisms that are largely responsible for rejection and loss of graft function. Within this context, a growing amount of evidence shows that alloreactive natural killer (NK) cells play a critical role in the immune response mechanisms elicited by the allograft. Killer immunoglobulin-like receptors (KIRs) are prominent mediators of NK cell alloreactivity.

Methods and findings

A cohort of 174 first cadaveric kidney allograft recipients and their donors were selected from a total cohort of 657 transplanted patients for retrospective immunogenetic analyses. Patients with HLA Class II mismatches were excluded. HLA Class I allele frequencies were compared among patients with chronic rejection, patients with stable graft function and a group of 2388 healthy controls. Activating and inhibitory KIR gene frequencies, KIR haplotypes, KIR-HLA ligand matches/mismatches and combinations of recipient KIRs and donor HLA Class I ligands were compared among patients with and without chronic rejection and a group of 221 healthy controls. Patients transplanted from donors homozygous for HLA-C1 antigens had a significantly higher risk for chronic rejection than patients transplanted from donors homozygous or heterozygous for HLA-C2 antigens or with epitopes belonging to the HLA-Bw4 ligand group. The Kaplan-Meier curves obtained by dividing the patients into 3 groups according to the presence or absence of one or both of the combinations of recipient KIRs and donor HLA ligands (rKIR2DL1/dHLA-C2 and rKIR3DL1/dHLA-Bw4) showed a significantly higher cumulative incidence of chronic rejection in the group of patients completely lacking these functional units. These patients showed a progressively stronger decline in modification of diet in renal disease-estimated glomerular filtration rate.

Conclusions

KIR genotyping should be performed at the time of enrolment of patients on the waiting list for organ transplantation. In our study, a significantly higher risk of chronic rejection after kidney transplantation was observed when recipient (r) and donor (d) pairs completely lacked the two functional rKIR-dHLA ligand combinations rKIR2DL1/dHLA-C2 and rKIR3DL1/dHLA-Bw4. This immunogenetic profile corresponds to low levels of NK cell inhibition. Therefore, patients with this high risk profile could benefit from immunosuppressive therapy aimed at reducing NK-cell cytotoxicity."xsd:string
http://purl.uniprot.org/citations/28686681http://purl.org/dc/terms/identifier"doi:10.1371/journal.pone.0180831"xsd:string
http://purl.uniprot.org/citations/28686681http://purl.uniprot.org/core/author"Lai S."xsd:string
http://purl.uniprot.org/citations/28686681http://purl.uniprot.org/core/author"Orru S."xsd:string
http://purl.uniprot.org/citations/28686681http://purl.uniprot.org/core/author"Cusano R."xsd:string
http://purl.uniprot.org/citations/28686681http://purl.uniprot.org/core/author"Melis M."xsd:string
http://purl.uniprot.org/citations/28686681http://purl.uniprot.org/core/author"Carcassi C."xsd:string
http://purl.uniprot.org/citations/28686681http://purl.uniprot.org/core/author"Serra M."xsd:string
http://purl.uniprot.org/citations/28686681http://purl.uniprot.org/core/author"Carta E."xsd:string
http://purl.uniprot.org/citations/28686681http://purl.uniprot.org/core/author"Alba F."xsd:string
http://purl.uniprot.org/citations/28686681http://purl.uniprot.org/core/author"Cappai L."xsd:string
http://purl.uniprot.org/citations/28686681http://purl.uniprot.org/core/author"Valentini D."xsd:string
http://purl.uniprot.org/citations/28686681http://purl.uniprot.org/core/author"Pani A."xsd:string
http://purl.uniprot.org/citations/28686681http://purl.uniprot.org/core/author"Arras M."xsd:string
http://purl.uniprot.org/citations/28686681http://purl.uniprot.org/core/author"Congeddu E."xsd:string
http://purl.uniprot.org/citations/28686681http://purl.uniprot.org/core/author"La Nasa G."xsd:string
http://purl.uniprot.org/citations/28686681http://purl.uniprot.org/core/author"Caocci G."xsd:string
http://purl.uniprot.org/citations/28686681http://purl.uniprot.org/core/author"Littera R."xsd:string
http://purl.uniprot.org/citations/28686681http://purl.uniprot.org/core/author"Piredda G."xsd:string
http://purl.uniprot.org/citations/28686681http://purl.uniprot.org/core/author"Frongia M."xsd:string
http://purl.uniprot.org/citations/28686681http://purl.uniprot.org/core/author"Loi V."xsd:string
http://purl.uniprot.org/citations/28686681http://purl.uniprot.org/core/author"Michittu M.B."xsd:string
http://purl.uniprot.org/citations/28686681http://purl.uniprot.org/core/author"Argiolas D."xsd:string
http://purl.uniprot.org/citations/28686681http://purl.uniprot.org/core/author"Maddi R."xsd:string
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