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.
Shulzhenko
N
N
Department of Pediatrics, Escola Paulista de Medicina, São Paulo, SP, Brazil.
Morgun
A
A
Zheng
X X
XX
Diniz
R V
RV
Almeida
D R
DR
Ma
N
N
Strom
T B
TB
Gerbase-DeLima
M
M
D053222:Fas Ligand Protein; D005786:Gene Expression Regulation; D006084:Graft Rejection; D053804:Granzymes; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics*; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000235:genetics*; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger; D054353:Perforin; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases