Details

Autor(en) / Beteiligte

• Littera, Roberto
• Piredda, Gianbenedetto
• Argiolas, Davide
• Lai, Sara
• Congeddu, Elena
• Ragatzu, Paola
• Melis, Maurizio
• Carta, Elisabetta
• Michittu, Maria Benigna
• Valentini, Donatella
• Cappai, Luisella
• Porcella, Rita
• Alba, Francesco
• Serra, Maria
• Loi, Valentina
• Maddi, Roberta
• Orrù, Sandro
• La Nasa, Giorgio
• Caocci, Giovanni
• Cusano, Roberto
• Arras, Marcella
• Frongia, Mauro
• Pani, Antonello
• Carcassi, Carlo
• Stepkowski, Stanislaw

Titel

KIR and their HLA Class I ligands: Two more pieces towards completing the puzzle of chronic rejection and graft loss in kidney transplantation

Ist Teil von

• PloS one, 2017-07, Vol.12 (7), p.e0180831-e0180831

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2017

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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. 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. 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.