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

The mechanisms underlying contractile dysfunction following heart tran splantation are poorly defined, To investigate the role of cytotoxic T cells (CTL) in cardiac transplant rejection, and during episodic cont ractile dysfunction, we performed a prospective study analyzing the ex pression of granzyme A and perforin, two functional markers of activat ed CTL. Sixteen consecutive patients were analyzed during the first ye ar posttransplantation, All patients received induction therapy with O KT-3 and received standard three-drug immunosuppression therapy, Rejec tion status was monitored using routine surveillance endomyocardial bi opsy and graded according to the ISHLT scale. Granzyme A and perforin mRNA were detected by reverse transcription PCR at the time of each ro utine biopsy. A total of 64/123 biopsies were positive for granzyme ex pression, while 38/123 samples were positive for perforin expression, LV function was monitored using M-mode derived fractional shortening a nd Doppler assessment of diastolic function (isovolumic relaxation tim e [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 i n diastolic function (chi(2)=6.4, P<0.02), but was not associated with systolic function. The presence of perforin message was not correlate d with functional changes or with rejection grade, but was associated with granzyme expression (chi(2)=9.11, P=0.0025), These studies sugges t that the presence of granzyme A message may be an important predicto r of graft function.