Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 562-566 |
| Number of pages | 5 |
| Journal | Diabetes |
| Volume | 51 |
| Issue number | 3 |
| State | Published - Jul 23 2002 |
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ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism
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Elevation of cytotoxic lymphocyte gene expression is predictive of islet allograft rejection in nonhuman primates. / Han, Dongmei; Xu, Xiumin; Pastori, Ricardo; Ricordi, Camillo; Kenyon, Norma S.
In: Diabetes, Vol. 51, No. 3, 23.07.2002, p. 562-566.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Elevation of cytotoxic lymphocyte gene expression is predictive of islet allograft rejection in nonhuman primates
AU - Han, Dongmei
AU - Xu, Xiumin
AU - Pastori, Ricardo
AU - Ricordi, Camillo
AU - Kenyon, Norma S
PY - 2002/7/23
Y1 - 2002/7/23
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=0036317695&partnerID=8YFLogxK
M3 - Article
C2 - 11872651
AN - SCOPUS:0036317695
VL - 51
SP - 562
EP - 566
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 3
ER -