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Transcriptional profiling to assess the clinical status of kidney transplants

Nature Clinical Practice Nephrology volume 2, pages 116–117 (2006)Cite this article

Over the past decade, we have investigated the hypothesis that a molecular diagnostic approach based on transcriptional profiling can refine the classification of kidney transplant biopsies. More recently, we have tested the idea that noninvasive transcriptional analysis of circulating blood cells and urine sediment cells can function not only as a surrogate for the invasive biopsy procedure, but can also provide predictive, diagnostic, and prognostic information.

Human renal1 and rodent cardiac allografts1,2 serve as magnets for activated recipient antidonor T cells.2 Activated host antidonor CD8+ T cells selectively kill donor cells, whereas naive T cells do not. These cytotoxic T lymphocytes (CTLs) home to and concentrate within human and rodent allografts during episodes of allograft rejection, and can therefore function as an indicator of rejection.2 Unfortunately however, the cumbersome cell-based methods used experimentally to detect activated host antidonor T cells do not enable routine clinical surveillance of renal allograft recipients. We have therefore begun investigating a molecular transcriptional profiling approach to clinical monitoring of renal allografts. The polymerase chain reaction (PCR) provides a sensitive and convenient means of rigorously quantifying the expression of numerous gene transcripts within a small sample of tissue. The development of DNA ARRAY technology provides another potent tool for transcriptional profiling. With the knowledge that host antidonor CTLs are concentrated within rejecting allografts, and that a carefully orchestrated succession of gene expression events facilitates the transition of naive T cells to proliferating effector T cells, we decided to investigate whether the intragraft expression of transcripts encoding the CTL cell-killing machinery and other components of T-cell activation could serve as an indicator of rejection. We found that these genes are expressed within rejecting, but not quiescent, mouse and human allografts.3,4,5 In fact, CTL-related genes are coordinately (simultaneously) expressed, thereby allowing the results to be authenticated by cross-checking the expression patterns of multiple genes.5 Many other T-cell activation transcripts (e.g. CD154) can be readily detected in rejecting, but not quiescent, human renal allografts.6

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Authors and Affiliations

  1. Professor of Medicine and Surgery, Co-Director of the Transplant Center and Director of the Transplant Research Center at Beth Israel Deaconess Medical Center, Boston, MA, USA

    Terry B Strom

  2. Chief of Nephrology and Transplant Medicine at New York-Presbyterian Hospital, and Stanton Griffis Distinguished Professor of Medicine at Weill Medical College of Cornell University, New York, NY, USA

    Manikkam Suthanthiran

Authors
  1. Terry B Strom
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  2. Manikkam Suthanthiran
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Correspondence to Terry B Strom.

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Competing interests

Dr Strom and Dr Suthanthiran hold patents in the area of molecular diagnosis and these patents pertain to some observations presented in this article.

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Strom, T., Suthanthiran, M. Transcriptional profiling to assess the clinical status of kidney transplants. Nat Rev Nephrol 2, 116–117 (2006). https://doi.org/10.1038/ncpneph0115

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