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

Autor: Paola Ragatzu, Maurizio Melis, Sandro Orru, E Congeddu, Carlo Carcassi, Valentina Loi, Sara Lai, R. Porcella, Maria Pina Serra, Roberto Cusano, Giorgio La Nasa, L Cappai, R Maddi, F Alba, Davide Argiolas, Roberto Littera, M Arras, Donatella Valentini, Mauro Frongia, Elisabetta Carta, Antonello Pani, Maria Benigna Michittu, Giovanni Caocci, Gianbenedetto Piredda
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
Graft Rejection
Male
Heredity
Physiology
Gene Expression
lcsh:Medicine
NK cells
Ligands
Biochemistry
Organ transplantation
Cellular types
Renal Transplantation
Medicine
lcsh:Science
Kidney transplantation
Kidney
Multidisciplinary
biology
Immune cells
Graft Survival
Receptors
KIR3DL1
Middle Aged
Killer Cells
Natural
Genetic Mapping
medicine.anatomical_structure
Creatinine
Histocompatibility
Receptors
KIR2DL1
White blood cells
Female
Anatomy
Unrelated Donors
Research Article
Glomerular Filtration Rate
Adult
medicine.medical_specialty
Cell biology
Blood cells
Immunology
Context (language use)
Surgical and Invasive Medical Procedures
Human leukocyte antigen
HLA-C Antigens
Major histocompatibility complex
Urinary System Procedures
03 medical and health sciences
Immune system
Antigen
Transplantation Immunology
Genetics
Cadaver
Humans
Transplantation
Homologous
Medicine and health sciences
Transplantation
Renal Physiology
Biology and life sciences
business.industry
Transplant Rejection
lcsh:R
Kidneys
Organ Transplantation
Renal System
medicine.disease
Kidney Transplantation
030104 developmental biology
Animal cells
Haplotypes
HLA-B Antigens
Case-Control Studies
biology.protein
Kidney Failure
Chronic
Clinical Immunology
lcsh:Q
Clinical Medicine
business
Biomarkers
Zdroj: PLoS ONE, Vol 12, Iss 7, p e0180831 (2017)
PLoS ONE
ISSN: 1932-6203
Popis: 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.
Databáze: OpenAIRE
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