APatients lacking a Kir-ligand of HLA group C1 or C2 have a Better Outcome after Umbilical cord Blood Transplantation

作者：Martinez Losada Carmen^*; Martin Carmen; Gonzalez Rafael; Manzanares Barbara; Garcia Torres Estefania; Herrera Concha

来源：Frontiers in Immunology, 2017, 8: 810.

DOI：10.3389/fimmu.2017.00810

• KIR
• KIR-ligand
• UCB-transplantion
• leukemia
• relapse

Donor natural killer (NK) cells can destroy residual leukemic cells after allogeneic hematopoietic stem cell transplantation. This effect is based on the interaction of killer-cell immunoglobulin-like receptors (KIR) of donor NK cells with ligands of the major histocompatibility complex found on the surface of the target cells. HLA-C1 subtypes provide the ligand for KIR2DL2 and KIR2DL3 and the HLA-C2 subtypes for KIR2DL1. We have studied the probability of relapse (PR) after single-unit unrelated cord blood transplantation (UCBT) in relation to the potential graft-vs.-leukemia effect mediated by NK cells present in the umbilical cord blood (UCB) by analyzing KIR-ligand and HLA-C typing of the receptor. Data from 33 consecutive patients given a single unit UCBT were included. We have considered two groups of patients based on the absence or the presence of one of the C-ligands for inhibitory KIR and the incompatibility HLA-C1/2 between UCB and patients. Group 1 (n = 21): the patient lacks a C-ligand for inhibitory KIR present in UCB NK cells, i.e., patients homozygous C1/C1 or C2/C2. Group 2 (n = 12): patients heterozygous C1/C2 in which KIR-mediated graft-vs.-leukemia effect is not expected (presence of both C-ligands for inhibitory KIR in the receptor). With a median follow-up post-UCBT of 93 months, patients with absence of a C-ligand for inhibitory KIRs (Group 1) showed a lower actuarial PR than patients with both C-ligands (group 2): 21 +/- 10 vs. 68 +/- 18% at 2 year and 36 +/- 13 vs. 84 +/- 14% at 5 years (p = 0.025), respectively. In patients with acute lymphoblastic leukemia, the 2-year PR was 36 +/- 21% for group 1 and 66 +/- 26% for 2 (p = 0.038). Furthermore, group 1 had a lower incidence of grades II-IV acute graft-vs.-host disease (p = 0.04). In the setting of UCBT, the absence of a C-ligand (C1 or C2) of inhibitory KIR in the patient is associated with lower PR, which is probably due to the graft-vs.-host leukemia effect caused by UCB NK cells that lack a ligand for the inhibitory KIR 2DL1/2DL2/2DL3.

• 出版日期2017-7-13