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 underg oing rejection. Methods. Quantitative reverse transcriptase-polymerase chain reaction was a pplied for mRNA detection in 29 endomyocardial biopsy specimens from 11 car diac 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 re jection (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 sign ificantly higher than in biopsy specimens without rejection. Any two of the three transcripts were increased in 100% of prerejection, in 92% of reject ion, 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 card iac allograft rejection, especially considering the predictive value for wa rning of impending acute rejection.