title: Blood monitoring of granzyme B and perforin expression after intestinal transplantation: considerations on clinical relevance.
abstract: 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.
authors.affiliation: Pathology Unit, Istituto Oncologico "F. Addarii," S. Orsola-Malpighi Hospital, Bologna University Bologna, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Altimari
authors.forename: Elisa
authors.initials: E
authors.lastname: Gruppioni
authors.forename: Elisa
authors.initials: E
authors.lastname: Capizzi
authors.forename: Alberto
authors.initials: A
authors.lastname: Bagni
authors.forename: Barbara
authors.initials: B
authors.lastname: Corti
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Fiorentino
authors.forename: Tiziana
authors.initials: T
authors.lastname: Lazzarotto
authors.forename: Augusto
authors.initials: A
authors.lastname: Lauro
authors.forename: Antonio Daniele
authors.initials: AD
authors.lastname: Pinna
authors.forename: Lorenza
authors.initials: L
authors.lastname: Ridolfi
authors.forename: Walter Franco
authors.initials: WF
authors.lastname: Grigioni
authors.forename: Antonia
authors.initials: A
authors.lastname: D'errico-Grigioni
mesh_terms: 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
chemical_list: D015415:Biomarkers; D054353:Perforin; D053804:Granzymes