Benefit of immune monitoring in heart transplant patients using ATP production in activated lymphocytes
published online 05 February 2010.
Background
Balancing immunosuppression to prevent rejection while minimizing infection or drug toxicity risk is a major challenge in heart transplantation. Therapeutic drug monitoring alone is inadequate to measure the immune response. An immune monitoring (IM) assay (ImmuKnow; Cylex, Columbia, MD) performed on peripheral blood measures adenosine triphosphatase (ATP) release from activated lymphocytes and may predict the immune state. Therefore, we sought to determine the utility of IM in heart transplant recipients.
Methods
Between November 2005 and July 2008, 296 heart transplant recipients had a total of 864 IM assays performed at 2 weeks to 10 years post-transplant and were correlated with infection and rejection events that occurred within 1 month after IM testing. All patients received standard triple-drug immunosuppressive therapy with tacrolimus, mycophenolate mofetil and corticosteroids, without induction therapy.
Results
There were 38 infectious episodes and 8 rejection episodes. The average IM score was significantly lower during infection than steady state (187 vs 280 ng ATP/ml, p < 0.001). The average IM score was not significantly different during rejection when compared with steady state (327 vs 280 ng ATP/ml, p = 0.35). Interestingly, 3 of 8 rejection episodes were antibody-mediated rejections and had hemodynamic compromise and, for these, the mean IM score was significantly higher than for steady-state patients (491 vs 280 ng ATP/ml, p < 0.001).
Conclusions
The non-invasive IM test appears to predict infectious risk in heart transplant patients. The association between high IM scores and rejection risk is inconclusive due to the small number of rejection episodes. Further studies with larger sample sizes for rejection episodes are required.
aDivision of Cedars-Sinai Heart Institute, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California
bDivision of Infectious Disease, Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California
cDivision of Cardiothoracic Surgery, Department of Surgery, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California
Reprint requests: Jon A. Kobashigawa, MD, Cedars-Sinai Heart Institute, 8700 Beverly Boulevard, Los Angeles, CA 90048. Telephone: 310-248-8300. Fax: 310-248-8333
ABSTRACT