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Long-term Kinetics of Intragraft Gene Signatures in Renal Allograft Tolerance Induced by Transient Mixed Chimerism.


ABSTRACT: BACKGROUND:Renal allograft tolerance (TOL) has been successfully induced in nonhuman primates (NHPs) and humans through the induction of transient mixed chimerism. To elucidate the mechanisms of TOL, we compared local immunologic responses in renal allografts with those in T-cell-mediated rejection (TCMR) and chronic antibody-mediated rejection (CAMR) in NHPs. METHODS:Using the NanoString nCounter platform, we retrospectively studied 52 mRNAs in 256 kidney allograft samples taken from NHP kidney recipients of donor BMT. No immunosuppression was given after 1-month post-donor BMT. Recipients who achieved TOL (n?=?13) survived for >1840 ± 1724 days with normal kidney function, while recipients with CAMR (n?=?13) survived for 899 ± 550 days with compromised graft function, and recipients with TCMR (n?=?15) achieved only short-term survival (132 ± 69 days). RESULTS:The most prominent difference between the groups was FOXP3, which was significantly higher in TOL than in CAMR and TCMR, both early (<1 y, P?

SUBMITTER: Matsunami M 

PROVIDER: S-EPMC6814550 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Long-term Kinetics of Intragraft Gene Signatures in Renal Allograft Tolerance Induced by Transient Mixed Chimerism.

Matsunami Masatoshi M   Rosales Ivy A IA   Adam Benjamin A BA   Oura Tetsu T   Mengel Michael M   Smith Rex-Neal RN   Lee Hang H   Cosimi A Benedict AB   Colvin Robert B RB   Kawai Tatsuo T  

Transplantation 20191101 11


<h4>Background</h4>Renal allograft tolerance (TOL) has been successfully induced in nonhuman primates (NHPs) and humans through the induction of transient mixed chimerism. To elucidate the mechanisms of TOL, we compared local immunologic responses in renal allografts with those in T-cell-mediated rejection (TCMR) and chronic antibody-mediated rejection (CAMR) in NHPs.<h4>Methods</h4>Using the NanoString nCounter platform, we retrospectively studied 52 mRNAs in 256 kidney allograft samples taken  ...[more]

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