Elevated immune monitoring as measured by increased adenosine triphosphate production in activated lymphocytes is associated with accelerated development of cardiac allograft vasculopathy after cardiac transplantation

Richard Cheng; Babak Azarbal; Aaron Yung; Jignesh K Patel; David H Chang; Frank Liou; Raj Makkar; Jon A Kobashigawa

doi:10.1016/j.healun.2016.03.016

Elevated immune monitoring as measured by increased adenosine triphosphate production in activated lymphocytes is associated with accelerated development of cardiac allograft vasculopathy after cardiac transplantation

J Heart Lung Transplant. 2016 Aug;35(8):1018-23. doi: 10.1016/j.healun.2016.03.016. Epub 2016 Mar 31.

Authors

Richard Cheng¹, Babak Azarbal², Aaron Yung¹, Jignesh K Patel¹, David H Chang¹, Frank Liou¹, Raj Makkar¹, Jon A Kobashigawa¹

Affiliations

¹ Division of Cardiology, Cedars-Sinai Heart Institute, Los Angeles, California, USA.
² Division of Cardiology, Cedars-Sinai Heart Institute, Los Angeles, California, USA. Electronic address: azarbalb@cshs.org.

PMID: 27138702
DOI: 10.1016/j.healun.2016.03.016

Abstract

Background: Elevated immune monitoring (IM), as measured by adenosine triphosphate (ATP) release from activated lymphocytes, has been suggested to represent an under-immunosuppressed state. Its association with the development of angiographic cardiac allograft vasculopathy (CAV) is unknown.

Methods: Patients transplanted between January 2007 and December 2011 with annual angiograms and at least 1 IM assay were included in the analysis. Peak IM scores were determined for each patient. Patients with peak IM in the highest quartile (Group 2) were compared with those with scores in the lower quartiles (Group 1). Mild disease was scored as Grade 1 (CAV1) and moderate or severe disease was scored as Grades 2 or 3 (CAV2/3).

Results: Two hundred forty patients were included. The mean age at transplant was 54.2 ± 12.1 years. Time to peak IM assay was 105.9 ± 44.1 days and average number of assays obtained per patient was 3.1 ± 1.8. Patients in the highest quartile (Group 2) had peak IM ≥446 ng ATP/ml. Mean clinical follow-up was 4.6 ± 1.7 years. CAV1 was observed in 86 of 180 (47.8%) patients in Group 1 and 39 of 60 (65.0%) in Group 2. Freedom from CAV1 was significantly lower in patients in Group 2 (log rank, p = 0.012). CAV2/3 occurred in 7 of 180 (3.7%) patients in Group 1 and 9 of 60 (15.0%) patients in Group 2. Freedom from CAV2/3 was significantly lower in patients in Group 2 (p = 0.003). In multivariate analysis elevated peak IM assay was still found to be associated with angiographic CAV (hazard ratio 1.647, confidence interval 1.020 to 2.661, p = 0.041).

Conclusion: Elevated peak IM, as measured by increased ATP production, in activated lymphocytes is associated with decreased freedom from angiographic CAV.

Keywords: Cylex; T-cell immune function; cardiac allograft vasculopathy; immunosuppression; transplant coronary artery disease.

MeSH terms

Adenosine Triphosphate
Allografts
Heart Transplantation*
Humans
Lymphocytes
Middle Aged
Monitoring, Immunologic

Substances

Adenosine Triphosphate