Two years' experience of acute rejection monitoring of intestinal transplant recipients by real-time PCR assessment of granzyme B and perforin up-regulation: considerations on diagnostic accuracy.
Granzyme B (GrB) and perforin are promising immunological markers to predict acute rejection of transplanted organs. Based on 2 years of experience with molecular monitoring on peripheral blood samples, we investigated the diagnostic accuracy of GrB/perforin gene up-regulation using real-time polymerase chain reaction (PCR) for prediction of acute cellular rejection (ACR) in intestinal transplantation recipients. Histology used as the reference standard. According to our definition of disease positivity (anything other than ACR score 0), GrB/perforin up-regulation showed 84% specificity but only 49% sensitivity. However, among the 26 false-negatives, 12 (46%) had an ACR score 1, which is indeterminate for rejection and no associated clinical manifestations; a further 10 (39%) had a score of 2 following rejection therapy (a confounder for GrB/perforin analysis). Thus only 4 (15%) false-negatives were actually associated with the onset of robust acute rejection. These data suggest that real-time PCR analysis for GrB/perforin up-regulation might play a role along with clinical criteria for detection of presymptomatic acute rejection episodes in intestinal recipients who require immediate endoscopy and pathological examination, especially during long-term follow-up.
Corti
B
B
Pathology Division, Felice Addarii Institute, S. Orsola-Malpighi Hospital, Bologna University School of Medicine, Viale Ercolani 4/2, 40138 Bologna, Italy.
Altimari
A
A
Gabusi
E
E
Pinna
A D
AD
Gruppioni
E
E
Lauro
A
A
Pirini
M G
MG
Fiorentino
M
M
Ridolfi
L
L
Grigioni
W F
WF
Grigioni
A D
AD
D005786:Gene Expression Regulation; D015971:Gene Expression Regulation, Enzymologic; D006084:Graft Rejection / Q000453:epidemiology* / Q000235:genetics; D053804:Granzymes; D006801:Humans; D007422:Intestines / Q000637:transplantation*; D008562:Membrane Glycoproteins / Q000235:genetics*; D054353:Perforin; D016133:Polymerase Chain Reaction / Q000379:methods*; D052899:Pore Forming Cytotoxic Proteins; D015203:Reproducibility of Results; D012697:Serine Endopeptidases / Q000235:genetics*
D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases