Donor NKG2C Copy Number: An Independent Predictor for CMV Reactivation After Double Cord Blood Transplantation.

Kai Cao,May Daher,Takuye Sekine,Katayoun Rezvani,Li Li,Rafet Basar,Amanda Olson,Elizabeth J Shpall,Chitra Hosing,Rohtesh S Mehta,Qing Wang,Ravi Pingali,Rima M Saliba,Weicheng Zhao,Uday Popat,Nathaniel Smith ,David Marín ,Richard E Champlin ,Betül Oran ,Gabriela Rondón

doi:10.3389/fimmu.2018.02444

Abstract

Cytomegalovirus (CMV) remains a major cause of morbidity following allogeneic hematopoietic stem cell transplant. Natural killer cells expressing NKG2C have been shown to play a role in the immune surveillance of human CMV. We studied NKG2C copy number in the donor graft and the risk of CMV reactivation after double umbilical cord blood transplantation (DUCBT) in 100 CMV seropositive DUCBT recipients and their corresponding cord blood (CB) grafts (n = 200). In the setting of DUCBT, the combined graft may contain 0–4 functional copies of NKG2C gene. Sixteen patients received a combined graft with 1 or 2 NKG2C copies and 84 patients were recipients of a combined graft with 3 or 4 NKG2C copies. The 6-month cumulative incidence of CMV reactivation for the two groups was 93.7 and 58.4%, respectively (p = 0.0003). In multivariate analysis, low NKG2C copies in the graft was an independent predictor of CMV reactivation (HR = 2.72, CI = 1.59–4.64; p < 0.0001). Our study points to an important role for donor NKG2C for protection against CMV reactivation after DUCBT. These novel findings may help identify patients at a higher risk of CMV reactivation after DUCBT. Donor NKG2C genotype may be used as a potential criterion in the algorithm for graft selection for DUCBT.

Highlights

Cytomegalovirus (CMV) is a member of the herpesviridae family and remains latent in the host cells after primary infection
NKG2C-expressing Natural killer (NK) cells have been linked to efficient recognition and elimination of CMV-infected cells [12, 13]
This observation, combined with studies reporting that the frequencies and regulation of NKG2C receptor expression is dependent on the gene copy number [19, 23], led us to hypothesize that the risk of CMV reactivation after double umbilical cord blood transplantation (DUCBT) could be directly influenced by the NKG2C copy number of the cord blood (CB) grafts

Summary

Introduction

Cytomegalovirus (CMV) is a member of the herpesviridae family and remains latent in the host cells after primary infection. Natural killer (NK) cells are known to be the first subset of lymphocytes to reconstitute after HSCT and play an important role in the early control of viral infections including CMV [7]. In the first year following allo-HSCT and cord blood (CB) transplantation, CMV reactivation induces expansion of a subset of mature “adaptive” NK cells, characterized as CD56dimCD16−NKG2C+ [12,13,14]. Taken together, these data point to a potential role for NKG2C in CMV recognition by NK cells

Methods

Results

Conclusion