2010 - Transplantomics and Biomarkers in Transplantation
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NOVEL APPLICATIONS FOR GENOMIC TECHNOLOGIES IN ORG
1.3 - DECONVOLUTING THE PERIPHERAL BLOOD TRANSCRIPTOME IN GRAFT REJECTION
Presenter: Minnie, Sarwal, Stanford, USA
Authors: Minnie Sarwal
DECONVOLUTING THE PERIPHERAL BLOOD TRANSCRIPTOME IN GRAFT REJECTION
Minnie Sarwal, Professor of Pediatrics and Immunology, Stanford University, Stanford, CA, USA
Minnie Sarwal, Professor of Pediatrics and Immunology, Stanford University, Stanford, CA, USA
Learning Objectives:
1. To discuss why the transplant field needs non-invasive means to predict for alloimmune injury to customize immunosuppression.
2. Microarrays as a means to discover new biomarkers for acute rejection.
3. The process of biomarker validation and cross-validation to develop a sensitive and specific predictor for graft rejection.
Early detection of acute renal allograft rejection (AR) remains a major clinical concern and unmet need in organ transplantation. Current blood and biofluid non-invasive screening and monitoring methods cannot detect early and subclinical graft injury. The clinical current practice only allows for the screening of established tissue rejection by the detection of inflammatory infiltrates on kidney biopsy samples, despite the fact that this methodology is limited by sampling variability, procedural morbidity and cost. The optimal monitoring approach in organ transplantation would be to non-invasively evaluate the risk for graft rejection before the onset of renal dysfunction such that immunosuppression could be proactively titrated to limit graft injury, and immunosuppression delivery could be customized to the patients’ immunosuppression threshold and thus limit patient morbidity from infectious and malignant complications.
Transcriptional profiling studies on biopsy specimens have confirmed that significant, coordinated expression changes occur in many genes with established AR. However, when these studies are applied to peripheral blood, the expression of the rejection response is substantially weaker than the corresponding response in the organ. The gene signature for AR is also influenced by biological and experimental variance, resulting in low signal to noise ratio. This talk discusses the issues in biomarker discovery in blood relating to AR and the results of a recent study that has identified a highly specific and sensitive gene-based biomarker panel in blood that can predict the onset of AR, well before any injury can be detected by organ dysfunction or graft biopsy. This approach provides a skeleton for further studies for biomarker discovery of disease phenotypes in organ transplantation.
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