Cytotoxic Lymphocyte Gene Expression in Peripheral Blood Leukocytes Correlates With Rejecting Renal Allografts1

Lm, Vasconcellos; Ad, Schachter; Zheng, Xiangqian; Shapiro, Michael; We, Harmon; Tb, Strom

doi:10.1097/00007890-199809150-00002

Cited by 177 publications

(121 citation statements)

References 17 publications

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“…Previous studies have confirmed that Granzyme B, a protein released by cytotoxic T lymphocytes, is associated with AR. [15][16][17][18][19] But did not note any significant differences about the cell types between diffuse C4d positive with focal C4d positive transplant glomerulitis and PTCitis. Similarly, also did not find whether there are cytotoxic T cells or regulatory T cells or both.…”

Section: Introductionmentioning

confidence: 99%

C4d deposition is associated with immune cells infiltrating in kidney allograft glomerulitis and peritubular capillaritis

Jin

2015

Renal Failure

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Section: Introductionmentioning

confidence: 99%

C4d deposition is associated with immune cells infiltrating in kidney allograft glomerulitis and peritubular capillaritis

Jin

2015

Renal Failure

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“…Peripheral blood was chosen as the sample source, as it provides the advantages associated with a non-invasive sampling procedure and has previously been shown to correspond to intragraft gene expression (13,14).…”

Section: Introductionmentioning

confidence: 99%

Serial Peripheral Blood Perforin and Granzyme B Gene Expression Measurements for Prediction of Acute Rejection in Kidney Graft Recipients

Simon

Opelz

Wiesel

et al. 2003

American Journal of Transplantation

101

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In the present study we investigated whether peripheral blood gene expression measurements may serve as an early and non-invasive tool to predict renal allograft rejection. Peripheral blood was collected twice weekly after transplantation and gene expression was measured using real-time polymerase chain reaction (PCR). Recipients with acute rejection (n = 17) had higher levels of perforin and granzyme B transcript on days 5-7, 8-10, 11-13, 17-19, 20-22, and 26-29, as compared to patients without rejection (n = 50, p < 0.05 in all cases). Rejection diagnosis using gene expression criteria, determined with receiver operating characteristic (ROC) curves, was possible 2-30 days before traditional diagnosis (median 11 days). The best diagnostic result was obtained from samples taken on days 8-10, with a specificity of 90% and a sensitivity of 82% for perforin, and a specificity of 87% and sensitivity of 72% for granzyme B. Decreases in perforin (p < 0.01) and granzyme B expression (p < 0.05) were observed after initiation of anti-rejection therapy. Our data indicate that gene expression measurement is a useful tool for the recognition of graft rejection in its earliest stages. Serial measurements could be implemented as a monitoring system to highlight patients at higher risk of rejection, making them candidates for biopsy or pre-emptive anti-rejection therapy.

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“…Activation of transcription of the cytotoxic lymphocyte (CL) genes granzyme B (GB), perforin, and fas ligand (FasL) in transplanted tissue has been reported to be intimately associated with acute renal allograft rejection in humans, particularly when two of the three genes are simultaneously upregulated (5,6). Recently, the elevation of CL gene (ECLG) expression in peripheral blood leukocytes (PBLs) has been correlated with human renal allograft rejection (7,8); however, no studies have been reported that analyze the potential utility of monitoring these markers to predict rejection before the onset of clinical symptoms.…”

mentioning

confidence: 99%

“…Semiquantitative RT-PCR has been used to detect the early phases of immune activation (7,8,17). Development of the LightCycler PCR instrument enables the user to monitor fluorescence of a PCR continuously in real-time and on-line, and it enables rapid, accurate, and sensitive quantification of nucleic acid.…”

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confidence: 99%

Elevation of Cytotoxic Lymphocyte Gene Expression Is Predictive of Islet Allograft Rejection in Nonhuman Primates

Han

Pastori

et al. 2002

Diabetes

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Hyperglycemia and increased insulin requirements are indicators of ongoing islet allograft rejection, but there are no methods to predict or confirm rejection. Elevation of cytotoxic lymphocyte (CL) gene expression in peripheral blood (PB) has been correlated with renal allograft rejection in humans, but no published study has assessed the utility of monitoring these markers as predictors of rejection before the onset of clinical symptoms. We have established quantitative real-time PCR methods to determine the levels of mRNA transcripts for the CL genes granzyme B (GB), perforin, and fas ligand in blood samples from rhesus and cynomolgus monkeys. Four rhesus monkeys with long-term islet allograft function were studied. Antirejection (anti-CD154) therapy was discontinued, and weekly PB samples were obtained to determine whether the levels of mRNA transcripts for CL genes correlated with and/or were predictive of islet allograft rejection, defined as a loss of C-peptide production. For all monkeys, elevation of CL gene expression preceded rejection by 83-197 days, with GB as the best predictor. Elevated mRNA levels were sustained for 2-2.5 months in three of four animals and 1 month in the other, thus suggesting that the testing of these parameters may have practical applications in clinical islet cell transplantation. Diabetes 51:562-566, 2002

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Cytotoxic Lymphocyte Gene Expression in Peripheral Blood Leukocytes Correlates With Rejecting Renal Allografts1

Abstract: 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.

Cited by 177 publications

References 17 publications

C4d deposition is associated with immune cells infiltrating in kidney allograft glomerulitis and peritubular capillaritis

C4d deposition is associated with immune cells infiltrating in kidney allograft glomerulitis and peritubular capillaritis

Serial Peripheral Blood Perforin and Granzyme B Gene Expression Measurements for Prediction of Acute Rejection in Kidney Graft Recipients

Elevation of Cytotoxic Lymphocyte Gene Expression Is Predictive of Islet Allograft Rejection in Nonhuman Primates

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