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A20—A Biomarker of Allograft Outcome: A Showcase in Kidney Transplantation

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The Multiple Therapeutic Targets of A20

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 809))

Abstract

Effective means to identify anti-donor immune activity before the transplant organ is damaged and rejected has been an important goal in transplantation research. Development of sensitive and non-invasive diagnostic methods that probe the immune status of the recipient as well as the resilience of the donor organ should enable personalized application of immunosuppressive drugs. With a non-invasive biomarker for rejection, it should be possible to selectively treat the patients that are rejecting the graft and wean the tolerant patients from immunosuppression. Although A20 is also expressed by activated CD4+ T cells and CD8+ T cells, its expression by mouse tubular cells has been shown to play an important role in protecting allografts from ischemia/reperfusion (I/R) injury and rejection. Using quantitative (real-time) reverse transcriptase polymerase chain reaction (qt-RT-PCR), we showed that expression levels of A20, hemeoxygenase (HO)-1, other anti-apoptotic molecules, granzyme-B (GZMB), perforin (PRF1), CD3 and other immune molecules in renal transplant biopsies, urinary cells and peripheral blood cells are predictive of transplantation outcomes. Measuring A20 at mRNA and protein levels has the potentiality to be diagnostic and prognostic of transplantation outcomes and thereby help in timely therapeutic interventions to prolong graft life.

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Authors and Affiliations

  1. The Transplant Institute, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA

    Gabor Bodonyi-Kovacs, Terry B. Strom & Prabhakar Putheti

  2. Immunogenetics and Transplantation Center, The Rogosin Institute, Weill Cornell Medical Center, New York, New York, USA

    Prabhakar Putheti

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  1. Gabor Bodonyi-Kovacs
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Correspondence to Prabhakar Putheti .

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  1. Department of Surgery, Division of Vascular and Endovascular Surgery, Center for Vascular Biology Research, Boston, Massachusetts, USA

    Christiane Ferran MD, PhD

  2. The Transplant Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA

    Christiane Ferran MD, PhD

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Bodonyi-Kovacs, G., Strom, T.B., Putheti, P. (2014). A20—A Biomarker of Allograft Outcome: A Showcase in Kidney Transplantation. In: Ferran, C. (eds) The Multiple Therapeutic Targets of A20. Advances in Experimental Medicine and Biology, vol 809. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-0398-6_7

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