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

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

HLA Class I allele frequencies in cadaveric kidney donors and healthy controls.

<p>HLA Class I allele frequencies in cadaveric kidney donors and healthy controls.</p

Glomerular filtration rate measured at 1, 6, 12, 24, 36, 48, 60 and 72 months after transplantation normalized to baseline levels measured at 1 month after transplantation.

<p>The error bar at each point represents the 95% Confidence Interval. The group of patients with low NK cell inhibition (completely lacking the two functional units rKIR2DL1/dHLA-C2 and rKIR3DL1/dHLA-Bw4) showed a statistically significant difference in comparison to the groups of patients with either partial or high NK cell inhibition; P = 3.5·10⁻¹⁴ obtained by calculating the area under the curve.</p

Donor HLA KIR ligands and KIR-HLA ligand combinations in recipient/donor pairs.

<p>Donor HLA KIR ligands and KIR-HLA ligand combinations in recipient/donor pairs.</p

KIR gene frequencies and KIR haplotypes in patients and 221 healthy controls.

<p>KIR gene frequencies and KIR haplotypes in patients and 221 healthy controls.</p

KIR-HLA ligand mismatches/matches in the 174 recipient/donor pairs.

<p>KIR-HLA ligand mismatches/matches in the 174 recipient/donor pairs.</p

Clinical and immunological characteristics of kidney transplant patients.

<p>Clinical and immunological characteristics of kidney transplant patients.</p

Serum creatinine levels after transplantation in three groups of patients stratified according to the presence or absence of combinations of recipient (r) KIRs and donor (d) HLA ligands: rKIR2DL1/dHLA-C2 and rKIR3DL1/dHLA-Bw4.

<p>Serum creatinine levels after transplantation in three groups of patients stratified according to the presence or absence of combinations of recipient (r) KIRs and donor (d) HLA ligands: rKIR2DL1/dHLA-C2 and rKIR3DL1/dHLA-Bw4.</p

Risk of chronic rejection according to the presence or absence of specific recipient (r) KIR and donor (d) HLA ligand combinations.

<p>Risk of chronic rejection according to the presence or absence of specific recipient (r) KIR and donor (d) HLA ligand combinations.</p