Natural killer cell function predicts severe infection in kidney transplant recipients

• Published in: American journal of transplantation Vol. 19; no. 1; pp. 166 - 177
• Main Authors: Dendle, Claire, Gan, Poh‐Yi, Polkinghorne, Kevan R., Ngui, James, Stuart, Rhonda L., Kanellis, John, Thursky, Karin, Mulley, William R., Holdsworth, Stephen
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.01.2019
• Subjects: Area Under Curve; CD16 antigen; CD3 antigen; CD56 antigen; Cell number; clinical research/practice; Cytomegalovirus; Cytomegalovirus (CMV); Cytomegalovirus Infections - blood; Cytomegalovirus Infections - complications; Cytotoxicity; Female; Health risk assessment; Humans; immunosuppression/immune modulation; Immunosuppressive Agents - pharmacology; Incidence; infection and infectious agents; infection and infectious agents – bacterial; infection and infectious agents – viral; Infections; infectious disease; kidney (allograft) function/dysfunction; Kidney Failure, Chronic - complications; Kidney Failure, Chronic - surgery; Kidney transplantation; Kidney Transplantation - adverse effects; kidney transplantation/nephrology; Kidney transplants; Killer Cells, Natural - cytology; Male; Middle Aged; Mycophenolic acid; natural killer (NK) cells/NK receptors; Natural killer cells; Postoperative Complications; Prospective Studies; Regression Analysis; Risk; ROC Curve; translational research/science; Transplant Recipients; infection and infectious agents - bacterial; translational research/science; immunosuppression/immune modulation; infectious disease; clinical research/practice; kidney transplantation/nephrology; kidney (allograft) function/dysfunction; natural killer (NK) cells/NK receptors; infection and infectious agents; infection and infectious agents - viral; Cytomegalovirus (CMV)
• ISSN: 1600-6135; 1600-6143
• DOI: 10.1111/ajt.14900

The aim of this study was to determine if natural killer cell number (CD3−/CD16±/CD56±) and cytotoxic killing function predicts severity and frequency of infection in kidney transplant recipients. A cohort of 168 kidney transplant recipients with stable graft function underwent assessment of natural killer cell number and functional killing capacity immediately prior to entry into this prospective study. Participants were followed for 2 years for development of severe infection, defined as hospitalization for infection. Area under receiver operating characteristic (AUROC) curves were used to evaluate the accuracy of natural killer cell number and function for predicting severe infection. Adjusted odds ratios were determined by logistic regression. Fifty‐nine kidney transplant recipients (35%) developed severe infection and 7 (4%) died. Natural killer cell function was a better predictor of severe infection than natural killer cell number: AUROC 0.84 and 0.75, respectively (P = .018). Logistic regression demonstrated that after adjustment for age, transplant function, transplant duration, mycophenolate use, and increasing natural killer function (odds ratio [OR] 0.82, 95% confidence interval [CI] 0.74‐0.90; P < .0001) but not natural killer number (OR 0.96, 95% CI 0.93‐1.00; P = .051) remained significantly associated with a reduced likelihood of severe infection. Natural killer cell function predicts severe infection in kidney transplant recipients. The measurement of natural killer cell function in a prospective cohort of kidney transplant recipients predicts the development of severe infection over 2 years of follow‐up.