Identification of a peripheral blood transcriptional biomarker panel associated with operational renal allograft tolerance.

Identification of a peripheral blood transcriptional biomarker panel associated with operational renal allograft tolerance. Research Abstract Details 

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Identification of a peripheral blood transcriptional biomarker panel associated with operational renal allograft tolerance. Abstract Text:

Sophie Brouard,Elaine Mansfield,Christophe Braud,Li Li,Magali Giral,Szu-chuan Hsieh,Dominique Baeten,Meixia Zhang,Joanna Ashton-Chess, Braudeau,Frank Hsieh,Alexandre Dupont,Annaik Pallier,Anne Moreau, Louis,Catherine Ruiz,Oscar Salvatierra,Jean-Paul Soulillou,Minnie Sarwal,

Long-term allograft survival generally requires lifelong immunosuppression (IS). Rarely, recipients display spontaneous "operational tolerance" with stable graft function in the absence of IS. The lack of biological markers of this phenomenon precludes identification of potentially tolerant patients in which IS could be tapered and hinders the development of new tolerance-inducing strategies. The objective of this study was to identify minimally invasive blood biomarkers for operational tolerance and use these biomarkers to determine the frequency of this state in immunosuppressed patients with stable graft function. Blood gene expression profiles from 75 renal-transplant patient cohorts (operational tolerance/acute and chronic rejection/stable graft function on IS) and 16 healthy individuals were analyzed. A subset of samples was used for microarray analysis where three-class comparison of the different groups of patients identified a "tolerant footprint" of 49 genes. These biomarkers were applied for prediction of operational tolerance by microarray and real-time PCR in independent test groups. Thirty-three of 49 genes correctly segregated tolerance and chronic rejection phenotypes with 99% and 86% specificity. The signature is shared with 1 of 12 and 5 of 10 stable patients on triple IS and low-dose steroid monotherapy, respectively. The gene signature suggests a pattern of reduced costimulatory signaling, immune quiescence, apoptosis, and memory T cell responses. This study identifies in the blood of kidney recipients a set of genes associated with operational tolerance that may have utility as a minimally invasive monitoring tool for guiding IS titration. Further validation of this tool for safe IS minimization in prospective clinical trials is warranted.

Identification of a peripheral blood transcriptional biomarker panel associated with operational renal allograft tolerance. Publishing Authors By Initials

S Brouard,E Mansfield,C Braud,L Li,M Giral,SC Hsieh,D Baeten,M Zhang,J Ashton-Chess,C Braudeau,F Hsieh,A Dupont,A Pallier,A Moreau,S Louis,C Ruiz,O Salvatierra,JP Soulillou,M Sarwal,

For similar surgical procedures, operative: transplantation: transplantation, homologous research abstracts see: surgical procedures, operative: transplantation: transplantation, homologous research

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Identification of a peripheral blood transcriptional biomarker panel associated with operational renal allograft tolerance. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Proceedings of the National Academy of Sciences of

VOLUME: 104

Page Numbers: 15448-53

Journal Abbreviation: Proc. Natl. Acad. Sci. U.S.A.

ISSN: 0027-8424

DAY: 14

MONTH: 09

YEAR: 2007

Identification of a peripheral blood transcriptional biomarker panel associated with operational renal allograft tolerance. Information

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LANGUAGE: eng

NlmUniqueID: 7505876

Identification of a peripheral blood transcriptional biomarker panel associated with operational renal allograft tolerance. Keywords Mesh Terms:

KEYWORDS: Transplantation, Homologous

MESH TERMS: genetics

Chemical & Substance for Abstract: Identification of a peripheral blood transcriptional biomarker panel associated with operational renal allograft tolerance. Information

Substance Name: Transforming Growth Factor beta

Registry Number: 0

Grant and Affiliation Information for Identification of a peripheral blood transcriptional biomarker panel associated with operational renal allograft tolerance.

AFFILIATION: Institut National de la Santé et de la Recherche Médicale, U643, Centre Hospitalier Universitaire de Nantes, Institut de Transplantation et de Recherche en Transplantation, and Université de Nantes, Faculte de Medicine, F-44000 Nantes, France.

Country: United States

AGENCY: United States NIAID

GRANT: U01 AI55795-02

ACRONYM: AI

MEDLINETA: Proc Natl Acad Sci U S A

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