Intragraft activation of genes encoding cytotoxic T lymphocyte effector molecules precedes the histological evidence of rejection in human cardiac transplantation.

BACKGROUND The purpose of the present study was to investigate transcripts of perforin, granzyme B, and Fas ligand (FasL) in heart transplants undergoing rejection. METHODS Quantitative reverse transcriptase-polymerase chain reaction was applied for mRNA detection in 29 endomyocardial biopsy specimens from 11 cardiac allograft recipients. RESULTS The mRNA levels of granzyme B, perforin, and FasL were higher (P<0.05) in biopsy specimens with rejection than in biopsy specimens without rejection (granzyme B, 0.53 vs. 0.09; perforin, 0.34 vs. 0; FasL, 0.57 vs. 0.36). In prerejection biopsy specimens, granzyme B and FasL levels were significantly higher than in biopsy specimens without rejection. Any two of the three transcripts were increased in 100% of prerejection, in 92% of rejection, and in 36% of no rejection biopsy specimens (P<0.04). CONCLUSIONS The assessment of intragraft levels of cytotoxic T lymphocyte effector molecule mRNA represents a valuable tool in the monitoring of cardiac allograft rejection, especially considering the predictive value for warning of impending acute rejection.

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