Natural Killer Cell Phenotypes and Clinical Outcomes in Pediatric Kidney Transplantation

Abstract

Background: Natural killer (NK) cells have gained recognition for playing an integral role in both alloimmunity and protective immunity, particularly viral infection control, in solid organ transplantation. Using data from the Clinical Trials in Organ Transplantation in Children (CTOTC) study entitled, "Immune Development in Pediatric Transplantation," (NCT00951353), we aimed to identify NK cell phenotypes that were associated with viral infection versus alloreactive events during the first year after transplantation. We also examined the relationship between NK cells with 7-year patient and allograft survival using the Scientific Registry for Transplant Recipients (SRTR) database.

Methods: A secondary analysis of peripheral blood mononuclear cells from 98 children aged 1-20 years old with kidney transplants was conducted using multiparameter flow cytometry for the following NK cell phenotypes: CD56^bright, CD56^dim, and CD56^negative. We associated these phenotypes with either viral infection or alloimmunity (de novo donor-specific antibody (dnDSA) development or acute rejection), using Fine-Gray subdistribution hazard models for competing risks. Secondary outcomes included allograft and patient survival.

Results: We demonstrated that specific baseline NK cell phenotypes obtained prior to transplantation may be associated with either viral infection or alloimmunity. An elevation in CD56^dim frequency was associated with an increased risk of infection, while an increase in CD56^negative absolute count was associated with an increased risk of an alloimmune event. NK cells were not associated with graft survival.

Conclusions: NK cell phenotyping may be a useful tool to help differentiate infectious from alloimmune risk.