Noninvasive diagnosis of cellular and antibody-mediated rejection by perforin and granzyme B in renal allografts.
A major milestone in transplantation would be the use of biomarkers to monitor rejection. We examined the association between perforin and granzyme-B gene expression detected in the peripheral blood of renal allograft recipients with cellular and antibody-mediated rejection. Furthermore, we judged the appropriateness of assigning negative rejection statuses to persons without a biopsy whose grafts were functioning well clinically. Of the 46 patients who completed the study, recipients with cellular rejection had higher perforin and granzyme-B levels compared with nonrejectors (p = 0.006). Interestingly, recipients with antibody-mediated rejection also had higher perforin and granzyme-B levels compared with nonrejectors (p = 0.04). Patients with high levels of granzyme B had a probability of rejecting that was 26.7 times greater than those patients with low levels of granzyme B. Perforin and granzyme B had sensitivities of 50% and specificities of 95% in predicting rejection (cutoff value = 140). Assigning negative rejection statuses to recipients without a biopsy whose grafts were functioning well did not have a major effect on the direction or significance of covariate values. This study suggests that perforin and granzyme-B gene expressions in peripheral blood are accurate in detecting both cellular and antibody-mediated rejection.
Veale
Jeffrey L
JL
Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA. jveale@mednet.ucla.edu
Liang
Leonard W
LW
Zhang
Qiuheng
Q
Gjertson
David W
DW
Du
Zeying
Z
Bloomquist
Erik W
EW
Jia
Juan
J
Qian
Lei
L
Wilkinson
Alan H
AH
Danovitch
Gabriel M
GM
Pham
Phuong-Thu T
PT
Rosenthal
J Thomas
JT
Lassman
Charles R
CR
Braun
Jonathan
J
Reed
Elaine F
EF
Gritsch
H Albin
HA
D000328:Adult; D000917:Antibody Formation / Q000276:immunology; D001706:Biopsy; D005260:Female; D015870:Gene Expression / Q000235:genetics; D006084:Graft Rejection / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology; D053804:Granzymes / Q000235:genetics*; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins / Q000235:genetics*; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012372:ROC Curve; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000706:statistics & numerical data; D012680:Sensitivity and Specificity; D013997:Time Factors
D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger; D054353:Perforin; D053804:Granzymes