Work

393: Presence of Activating KIR Genotypes Influences Cytomegalovirus (CMV) Reactivation as Detected by Q-PCR in HCT Recipients

Year: 2008

Type: article

Abstract: Killer Ig-like receptor (KIR) is a cluster of natural killer cell receptors presented by T cells and natural killer (NK) cells. The compatibility of these receptors between the donor and the recipient plays a role in hematopoietic cell transplantation (HCT) for either activating (aKIR) or inhibitory KIRs. Some aKIRs bind only weakly to HLA class I and the natural ligands remain undetermined whereas the inhibitory KIRs bind HLA class I molecules with specificity for defined alleles of HLA-C, HLA-B, or HLA-A. It has been suggested that the donor KIR genotype influences the rate of CMV infection and, more particularly, that aKIR genes are inversely associated with CMV reactivation (Cook et al Blood 2006; 107: 1230–32; Chen et al. BMT 2006; 38: 437–44). In this study, a cohort of 92 non T-cell depleted subjects, who had received a matched unrelated or HLA identical related donor, were analyzed for inhibitory KIR ligands and KIR genotypes obtained using a multiplex PCR-SSP method. All recipients were at risk for CMV reactivation which was monitored bi-weekly by Q-PCR on plasma DNA. Results: Two groups, those with CMV reactivation (n = 68) vs No CMV (n = 24), were compared for the presence of KIR determinants and analyzed using a contingency table with Chi2 test for probability values. An increased number of aKIR genes in the donor, either involving an A haplotype, carrying a single aKIR gene, or the AB and BB haplotypes carrying more than one aKIRs, was significantly associated with a reduction of CMV reactivation (p = 0.0438). In addition, using a previously described algorithm for scoring KIR determinants in donor and recipient (Sun et al. BMT 2005; 56: 525–530), values >0, associated with more aKIRs in the donor but not in the recipient, were associated with significantly less CMV reactivation (62% VS 85%, p = 0.0372). When the recipients were analyzed for HLA-Cw KIR ligand group1 or 2, there was no significant association with CMV reactivation. This was still true when HLA class I mismatched donor-recipient pairs were excluded. Conclusion: In the HCT setting, aKIR genes in donor cells protect the recipient from CMV reactivation but the HLA-Cw allotype of the recipient does not predict CMV infection.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.bbmt.2007.12.403