Cytotoxic lymphocyte gene expression in peripheral blood leukocytes correlates with rejecting renal allografts.
BACKGROUND
We have shown previously that heightened expression of the cytotoxic lymphocyte (CL) effector genes perforin (P), granzyme B (GB), and Fas ligand (FasL), is closely correlated with acute allograft rejection, particularly when two or more target genes are up-regulated.


METHODS
We used quantitative reverse transcription-polymerase chain reaction to analyze CL gene expression from peripheral blood leukocytes (PBLs) and renal allograft biopsies in 31 paired samples of PBLs and renal tissue from 25 renal allograft recipients. Our aims were (1) to determine whether the expression of CL gene expression in PBLs correlates with expression of these genes in renal allograft biopsy tissue and (2) to determine whether CL gene expression in PBLs correlates with the histological diagnosis.


RESULTS
Coordinate gene expression in PBLs and acutely rejecting allografts was found in 9/11 (82%) for P, 07/11 (64%) for GB, and 10/11 (91%) for FasL. Coordinate absence was found in 15/20 (75%) for P, 17/20 (85%) for GB, and 16/20 (80%) for FasL in nonrejecting allografts. Furthermore, up-regulation of any two genes in PBLs correlated with pathological diagnosis of rejection with excellent positive (100%) and negative (95%) predictive values.


CONCLUSIONS
Coordinate CL gene expression in PBLs and the allograft is usually detected. CL gene expression in PBLs is closely associated with a pathologic diagnosis of rejection. CL gene expression in PBLs may serve as a noninvasive method of monitoring for renal allograft rejection.
Vasconcellos
L M
LM
Harvard Medical School, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.
Schachter
A D
AD
Zheng
X X
XX
Vasconcellos
L H
LH
Shapiro
M
M
Harmon
W E
WE
Strom
T B
TB
Schachter
D
D
D000328:Adult; D002648:Child; D053222:Fas Ligand Protein; D015870:Gene Expression; D006084:Graft Rejection / Q000276:immunology*; D053804:Granzymes; D006801:Humans; D016030:Kidney Transplantation / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012697:Serine Endopeptidases / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases