mRNA Biomarkers in Renal Allograft Protocol Biopsies Detected by the Nanostring Platform Predict Tolerance in Non-Human Primates.
1Department of Surgery, Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA
2Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
3Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada
Meeting: 2017 American Transplant Congress
Abstract number: A118
Keywords: Gene expression, Kidney transplantation, Primates, Tolerance
Session Information
Session Name: Poster Session A: Diagnostics/Biomarkers Session I
Session Type: Poster Session
Date: Saturday, April 29, 2017
Session Time: 5:30pm-7:30pm
Presentation Time: 5:30pm-7:30pm
Location: Hall D1
Background. Renal allograft tolerance has been achieved in some but not all MHC mismatched kidneys in non-human primates (NHPs) and humans after induction of transient mixed chimerism. Reliable tolerance biomarkers are critically important to identify the recipients in whom immunosuppressive medications can be safely withdrawn.
Method. Using the NanoString platform, we retrospectively quantitated mRNA expression of 67 genes in 228 kidney allograft formalin fixed paraffin embedded samples taken from NHPs recipients that had received combined kidney and donor bone marrow transplantation (DBMT).
Results. Protocol renal allograft biopsies taken early after DBMT (day 30-120) from recipients that achieved tolerance (TOL, n=11, >1995±557 days) showed significantly higher mRNA expression of Foxp3, BCL2, EPO, GATA3, RPS6KB1 and TEK compared with biopsies from recipients that developed chronic antibody-mediated rejection (cAMR, n=11, 850±134 days) or acute T cell mediated rejection (TCMR, n=9, 109±22 days) (Fig. 1A). These initially high biomarkers in TOL slowly declined over several years, and the timing of assays appeared important to compare TOL and non-TOL recipients (Fig. 1B). mRNA of inflammatory cytokines such as IFNG, CXCL11, FCGR3A, GNLY and GZMB, and Th2 related cytokines such as CD4, IL1RL1 and IL4 were higher in TCMR compared with those in TOL and cAMR recipients. The ROC curve of Foxp3/GZMB and FOXP3/GNLY ratios reliably predicted TOL, cAMR vs. TCMR (AUC 0.91, p=0.002) and TOL vs. cAMR (AUC 0.88, p=0.015) respectively (Fig. 1C).
Conclusions. mRNA expression in the renal allograft detected by the NanoString platform appear to provide a reliable measure of long-term outcome of the renal allograft in mixed chimerism protocols.
CITATION INFORMATION: Matsunami M, Oura T, Rosales I, Smith R.-N, Adam B, Mengel M, Cosimi A, Colvin R, Kawai T. mRNA Biomarkers in Renal Allograft Protocol Biopsies Detected by the Nanostring Platform Predict Tolerance in Non-Human Primates. Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:
Matsunami M, Oura T, Rosales I, Smith R-N, Adam B, Mengel M, Cosimi A, Colvin R, Kawai T. mRNA Biomarkers in Renal Allograft Protocol Biopsies Detected by the Nanostring Platform Predict Tolerance in Non-Human Primates. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/mrna-biomarkers-in-renal-allograft-protocol-biopsies-detected-by-the-nanostring-platform-predict-tolerance-in-non-human-primates/. Accessed November 22, 2024.« Back to 2017 American Transplant Congress