THE RELATIONSHIP OF GRANZYME A AND PERFORIN EXPRESSION TO CARDIAC ALLOGRAFT REJECTION AND DYSFUNCTION1

Publisher Website
Google Scholar
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 (X2=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 (X2=9.11,P=0.0025). These studies suggest that the presence of granzyme A message may be an important predictor of graft function.

This publication has 0 references indexed in Scilit: