Pre-Transplant Immune Cell Function Assay as a Predictor of Early Cardiac Allograft Rejection

Abstract

Purpose ImmuKnow, an immune cell function assay that quantifies overall immune system activity can assist in post-transplant immunosuppression adjustment. The utility of pretransplant ImmuKnow results representing a patient's baseline immune system activity is unknown. We sought to assess if pretransplant ImmuKnow results are predictive of rejection at the time of first biopsy in a cardiac transplant population.. Methods 81 cardiac transplant patients with pre-transplant ImmuKnow results (out of 110 total transplant patients) were identified. ImmuKnow results were analyzed according to the clinical interpretation ranges (low, medium, high activity). Pre-transplant clinical characteristics, induction immunosuppression use, early postoperative tacrolimus levels (Day 7 post transplant), and first endomyocardial biopsy results were collected for all patients. Logistic regression was used to estimate the association of the pre-transplant ImmunKnow group with clinically significant early rejection (≥ 1R/2), and to determine if the association was modified by the use of induction therapy and early tacrolimus levels. Results Significant early rejection was found in 15 patients (18.5%). Early rejection occurred in 0/15 patients with low pretransplant ImmuKnow levels vs. 15/64 patients with moderate or high pre-transplant ImmunoKnow levels (p=0.04). Induction immunosuppression was used for 26 patients (32.1%). The most common reason for induction was dual organ transplantation. Of the 55 patients without induction immunosuppression, 13 had rejection (23.6%). The mean ImmuKnow level in the non-rejection group was 391 ng/ml of ATP compared to 516 ng/ml of ATP for those with rejection (p=0.06). Lower pretransplant ImmuKnow levels among non-rejection patients was not diminished when controlling for tacrolimus level. Conclusion Patients with low pre-transplant ImmunoKnow levels had a lower risk of early rejection when compared with patients with medium or high levels. After adjusting for tacrolimus level, this relationship was maintained. Our study suggests a possible utility in performing pretransplant ImmunoKnow to identify patients at-risk for early rejection who may benefit from intensified upfront immunosuppression.