Blood monitoring of granzyme B and perforin expression after intestinal transplantation: considerations on clinical relevance.
BACKGROUND
The use of biomarkers for rejection monitoring represents a major goal in intestinal transplantation. We analyzed the blood expression of Granzyme B (GB) and Perforin (PF) in the following pathological conditions after intestinal transplantation: acute rejection (AR), Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infection, and posttransplant lymphoproliferative disease (PTLD). The diagnostic accuracy and the clinical utility of these tests are finally discussed.


METHODS
GB and PF levels were measured by real time polymerase chain reaction on peripheral blood samples from 32 intestinal recipients. Blood samples (n=494) after comparison of clinical, histological, and microbiological data were assigned to the following groups: normal (n=307), AR (n=30), EBV infection (n=107), CMV infection (n=25), and PTLD (n=25).


RESULTS
Mean levels of GB and PF in the AR (GB=279.7; PF=256.7), PTLD (GB=199; PF=185.9), EBV (GB=133.2; PF=143.7), and CMV (GB=151.3; PF=144) groups were significantly higher than in the normal group (GB=100.1; PF=101.1) (all P<0.05, except for PF in CMV infection). The best accuracy was obtained for the diagnosis of AR with sensitivity and specificity of 80% and 79% for GB and 70% and 79% for PF, respectively. The area under the receiver-operator characteristics curve was 0.87 for GB and 0.82 for PF.


CONCLUSIONS
GB and PF are diagnostic molecular markers of AR. GB and PF blood levels are also increased in case of viral infections or PTLD. Serial blood testing for GB and PF might be predictive of early intestinal graft dysfunction and should be interpreted in the context of the histological and virological analyses.
Altimari
Annalisa
A
Pathology Unit, Istituto Oncologico "F. Addarii," S. Orsola-Malpighi Hospital, Bologna University Bologna, Italy.
Gruppioni
Elisa
E
Capizzi
Elisa
E
Bagni
Alberto
A
Corti
Barbara
B
Fiorentino
Michelangelo
M
Lazzarotto
Tiziana
T
Lauro
Augusto
A
Pinna
Antonio Daniele
AD
Ridolfi
Lorenza
L
Grigioni
Walter Franco
WF
D'errico-Grigioni
Antonia
A
D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D003586:Cytomegalovirus Infections / Q000097:blood / Q000175:diagnosis*; D020031:Epstein-Barr Virus Infections / Q000097:blood / Q000175:diagnosis*; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000097:blood / Q000175:diagnosis*; D053804:Granzymes / Q000097:blood* / Q000378:metabolism; D006801:Humans; D007422:Intestines / Q000637:transplantation*; D054066:Leukemia, Large Granular Lymphocytic; D008875:Middle Aged; D016377:Organ Transplantation; D054353:Perforin / Q000097:blood* / Q000378:metabolism; D011183:Postoperative Complications / Q000097:blood / Q000175:diagnosis / Q000821:virology; D012680:Sensitivity and Specificity
D015415:Biomarkers; D054353:Perforin; D053804:Granzymes