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Updated: Aug 8, 2026
Murine Heterotopic Heart Transplant Technique
Published on: July 8, 2014
The relationship of granzyme A and perforin expression to cardiac allograft rejection and dysfunction
1Division of Cardiovascular Medicine, Stanford University School of Medicine, California 94305, USA.
Insights
Cytotoxic T cells (CTL) expressing granzyme A may predict heart transplant rejection and dysfunction. Granzyme A, a marker of activated CTL, was linked to decreased diastolic function, suggesting its role in graft health.
Area of Science:
- Cardiology
- Immunology
- Transplantation
Background:
- Contractile dysfunction after heart transplantation is not well understood.
- The role of cytotoxic T cells (CTL) in cardiac transplant rejection and dysfunction requires further investigation.
Purpose of the Study:
- To explore the involvement of granzyme A and perforin, markers of activated CTL, in cardiac transplant rejection and contractile dysfunction.
- To determine if granzyme A or perforin expression predicts graft function post-heart transplantation.
Main Methods:
- Prospective analysis of 16 heart transplant patients during their first year post-transplantation.
- Monitoring rejection status via endomyocardial biopsy and ISHLT grading.
- Assessing granzyme A and perforin mRNA expression using reverse transcription PCR.
- Evaluating left ventricular (LV) function through fractional shortening and diastolic parameters (IVRT, P1/2).
Main Results:
- Granzyme A mRNA was detected in 64/123 biopsies and was significantly associated with rejection grade (P = 0.001).
- Granzyme A expression correlated with impaired diastolic function (P < 0.02) but not systolic function.
- Perforin mRNA was found in 38/123 samples and correlated with granzyme A expression (P = 0.0025) but not directly with functional changes or rejection grade.
Conclusions:
- Granzyme A expression in heart transplant recipients is linked to rejection and impaired diastolic function.
- Granzyme A may serve as a valuable early predictor of cardiac allograft function and rejection.
Abstract:
The mechanisms underlying contractile dysfunction following heart transplantation are poorly defined. To investigate the role of cytotoxic T cells (CTL) in cardiac transplant rejection, and during episodic contractile dysfunction, we performed a prospective study analyzing the expression of granzyme A and perforin, two functional markers of activated CTL. Sixteen consecutive patients were analyzed during the first year posttransplantation. All patients received induction therapy with OKT-3 and received standard three-drug immunosuppression therapy. Rejection status was monitored using routine surveillance endomyocardial biopsy and graded according to the ISHLT scale. Granzyme A and perforin mRNA were detected by reverse transcription PCR at the time of each routine biopsy. A total of 64/123 biopsies were positive for granzyme expression, while 38/123 samples were positive for perforin expression. LV function was monitored using M-mode derived fractional shortening and Doppler assessment of diastolic function (isovolumic relaxation time [IVRT] and pressure half-time [P1/2]). As expected, the presence of granzyme A message was associated with rejection score (ANOVA, P = 0.001). In addition, granzyme A expression was correlated with a decrease in diastolic function (chi 2 = 6.4, P < 0.02), but was not associated with systolic function. The presence of perforin message was not correlated with functional changes or with rejection grade, but was associated with granzyme expression (chi 2 = 9.11, P = 0.0025). These studies suggest that the presence of granzyme A message may be an important predictor of graft function.
