Pre-transplant immune cell function assay as a predictor of early cardiac allograft rejection

Abstract

Introduction: ImmuKnow, an immune cell function assay that quantifies overall immune system activity can assist in post-transplant immunosuppression adjustment. However, the utility of pre-transplant ImmuKnow results representing a patient's baseline immune system activity is unknown. This study sought to assess if pre-transplant ImmuKnow results are predictive of rejection at the time of first biopsy in our cardiac transplant population.

Methods: This is a single center, retrospective observational study of consecutive patients from January 1, 2018 to October 1, 2020 who underwent orthotopic cardiac transplantation at NYU Langone Health. Patients were excluded if a pre-transplant ImmuKnow assay was not performed. ImmuKnow results were categorized according to clinical interpretation ranges (low, moderate, and high activity), and patients were divided into two groups: a low activity group versus a combined moderate-high activity group. Pre-transplant clinical characteristics, induction immunosuppression use, early postoperative tacrolimus levels, and first endomyocardial biopsy results were collected for all patients. Rates of clinically significant early rejection (defined as rejection ≥ 1R/1B) were compared between pre-transplant ImmuKnow groups.

Results: Of 110 patients who underwent cardiac transplant, 81 had pre-transplant ImmuKnow results. The low ImmuKnow activity group was comprised of 15 patients, and 66 patients were in the combined moderate-high group. Baseline characteristics were similar between groups. Early rejection occurred in 0 (0%) patients with low pre-transplant ImmuKnow levels. Among the moderate- high pre-transplant ImmuKnow group, 16 (24.2%) patients experienced early rejection (P = .033). The mean ImmuKnow level in the non-rejection group was the 364.9 ng/ml of ATP compared to 499.3 ng/ml of ATP for those with rejection (P = .020).

Conclusion: Patients with low pre-transplant ImmuKnow levels had lower risk of early rejection when compared with patients with moderate or high levels. Our study suggests a possible utility in performing pre-transplant ImmuKnow to identify patients at-risk for early rejection who may benefit from intensified upfront immunosuppression as well as to recognize those where slower calcineurin inhibitor initiation may be appropriate.

Keywords: ImmuKnow; rejection; transplant.