A Risk Score Using a Cell-based Assay Predicts Long-term Over-immunosuppression Events in Kidney Transplant Recipients

Abstract

Background: Infections and cancer are major causes of premature death in organ recipients. However, there have been few advances in personalized immunosuppressive therapy. We previously reported that a cell-based assay measuring CD14 + 16 + tumor necrosis factor-α + monocytes after peripheral blood mononuclear cell (PBMC) incubation with Epstein-Barr virus peptides has a high sensitivity for detecting over-immunosuppression (OIS) events in kidney recipients in the short term. We aimed to develop a risk score for predicting long-term events.

Methods: We studied 551 PBMC samples from 118 kidney recipients. Following random allocation to a testing and training set, we derived a risk function for the delineated tertiles of low, intermediate, and high risk of OIS based on age and CD14 + 16 + tumor necrosis factor-α + cells.

Results: Patients were followed for a median of 6.3 y (25th-75th percentiles: 3.7-8.3 y). Of these, 40 (34%) experienced an OIS event. The validation indicated that the risk score was well calibrated, with an absolute risk of 21%, 41%, and 61% in the low-, intermediate-, and high-risk categories, respectively ( P = 0.03). In sensitivity analyses, the risk score was robust to alternative definitions of OIS ranging from mild to severe. In particular, when restricted to life-threatening OIS, the proportion of events varied from 5% to 27% among the low- and high-risk categories, respectively ( P = 0.01).

Conclusions: Using a combination of age and in vitro PBMC response to Epstein-Barr virus peptides allows a substantial shift in the estimated risk of OIS events.