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

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.

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.

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).

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.