Recipient and Donor KIRs Ligands Match Prevents CMV Reactivation Post-Haploidentical T Cell-Replete Transplantation

Licensed NK cells have been demonstrated to have anti-cytomegalovirus (CMV) activity. We prospectively analysed the HLA typing of donor-recipient pairs and the KIR typing of the donors in 180 leukaemia patients to assess the predictive roles of licensed NK cells and donor-activating KIR genes on CMV reactivation post-T cell-replete haplo-SCT. Multivariate analysis showed that donor and recipient KIR ligand-ligand graft-versus-host direction or host-versus-graft direction mismatch were associated with the incidence of CMV reactivation [HR=1.663, 95%CI, 1.161-2.383, P=0.006] and refractory CMV infection [HR=2.34, 95%CI, 1.28-4.27, P=0.006] post-haploidentical T cell-replete transplantation. Donor and recipient KIR ligand-ligand match decreased CMV reactivation (51.65% [46.67, 56.62%] vs. 75.28% [70.87, 79.69%], P=0.012), refractory CMV infection (17.58% [13.77, 21.40%] vs. 35.96% [31.09, 40.82%], P=0.004) and CMV disease (3.30% [1.51, 5.08%] vs. 11.24% [8.04, 14.43%], P=0.024), respectively. Meanwhile, there was a significantly increased risk of CMV reactivation in patients who accepted a KIR2DS2-positive donor compared those who accepted a KIR2DS2-negative donor (80% [71.93, 88.07%] vs. 63.87% [60.18, 67.56%], P=0.039), especially in recipient HLA-C1/C2 and donor HLA-C1C2 with KIR2DL1/2DL2/2DL3/2DS2 genotype (100%).

Conclusions: These findings suggested that donor and recipient KIR ligand-ligand match might promote the NK cell licensing process, thereby increasing NK cell-mediated protection against CMV reactivation. However, roles of donor positivity for the KIR2DS2 against CMV reactivation need to be further explored in T cell-replete haplo-SCT.