Abstract 14749: Use of Rho-associated coiled-coil forming kinase (ROCK) Activity for Rejection Surveillance in Heart Transplant Recipients
Background: Acute rejection and consequences remain a major factor limiting long-term survival despite continued advancement in the use of immunosuppression. Routine surveillance with invasive, expensive endomyocardial biopsy (EMB) remains the gold standard for the detection of acute rejection . Gene-expression profiling has good sensitivity for cellular rejection but has limitations. The ROCK activity is elevated during inflammatory conditions and in heart failure. We aimed to determine whether ROCK activity in peripheral leukocytes is increased in patients with acute rejection, prior to the onset of specific clinical findings.
Methods: A prospective study was performed to determine the association between leukocyte ROCK activity and graft rejection. Subjects were enrolled immediately after cardiac transplantation. All subjects underwent standard of care scheduled surveillance right heart catheterization, endomyocardial biopsy, and a collection of peripheral blood for leukocytes. The ROCK activity in leukocytes during each visit was measured using a specific antibody against phosphorylated myosin-binding subunit (p-MBS) of myosin light chain phosphatase, and was compared with endomyocardial biopsy grading using ISHLT criteria .
Results: 41 adult heart transplant recipients with 140 visits were included, 1 with acute cellular rejection (ACR), 1 with antibody-mediated rejection (AMR), and 2 with Quilty lesions. 33 were male, mean age was 52 years, mean duration of 1.5 years since transplant. The ROCK activity was found to be elevated in patients prior to have clinical findings with ACR (grade 3R, 9.1 fold induction), AMR (2.0 fold induction), compared with patient without graft rejections (grade 0R or 1R, 0.89±0.20). The ROCK activity was not elevated in patients with Quilty lesions.
Conclusions: Peripheral leukocytes ROCK activity is increased in patients with graft rejection, prior to any specific clinical findings, and is correlated with cardiac biopsy grade. Therefore, monitoring leukocyte ROCK activity may be clinically useful in detecting early graft rejection in heart transplant patients. However, more patients and further longitudinal studies are required to assess its diagnostic and prognostic value in clinical practice.
Author Disclosures: D.Y. Zhang: None. S.E. Fedson: None. P.P. Ongusaha: None. G.T. Sayer: None. G.H. Kim: None. N. Uriel: None. M. Knapp: None. J.K. Liao: None.
- © 2014 by American Heart Association, Inc.