Elevation of cytotoxic lymphocyte gene expression is predictive of islet allograft rejection in nonhuman primates

Research output: Contribution to journalArticle

28 Citations (Scopus)

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 languageEnglish
Pages (from-to)562-566
Number of pages5
JournalDiabetes
Volume51
Issue number3
StatePublished - Jul 23 2002

Fingerprint

Primates
Allografts
Lymphocytes
Gene Expression
Macaca mulatta
Messenger RNA
Granzymes
Islets of Langerhans Transplantation
Fas Ligand Protein
Macaca fascicularis
C-Peptide
Cell Transplantation
Islets of Langerhans
Hyperglycemia
Genes
Haplorhini
Real-Time Polymerase Chain Reaction
Insulin
Kidney
Therapeutics

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

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 journalArticle

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