Development and validation of a peripheral blood mRNA assay for the assessment of antibody-mediated kidney allograft rejection: A multicentre, pros…

A new interesting article has been published in EBioMedicine. 2019 Jul 26. pii: S2352-3964(19)30463-3. doi: 10.1016/j.ebiom.2019.07.028. and titled:

Development and validation of a peripheral blood mRNA assay for the assessment of antibody-mediated kidney allograft rejection: A multicentre, pros…

Authors of this article are:

Van Loon E, Gazut S, Yazdani S, Lerut E, de Loor H, Coemans M, Noël LH, Thorrez L, Van Lommel L, Schuit F, Sprangers B, Kuypers D, Essig M, Gwinner W, Anglicheau D, Marquet P, Naesens M.

A summary of the article is shown below:

BACKGROUND: Antibody-mediated rejection, a leading cause of renal allograft graft failure, is diagnosed by histological assessment of invasive allograft biopsies. Accurate non-invasive biomarkers are not available.METHODS: In the multicentre, prospective BIOMARGIN study, blood samples were prospectively collected at time of renal allograft biopsies between June 2011 and August 2016 and analyzed in three phases. The discovery and derivation phases of the study (N = 117 and N = 183 respectively) followed a case-control design and included whole genome transcriptomics and targeted mRNA expression analysis to construct and lock a multigene model. The primary end point was the diagnostic accuracy of the locked multigene assay for antibody-mediated rejection in a third validation cohort of serially collected blood samples (N = 387). This trial is registered with ClinicalTrials.gov, number NCT02832661.FINDINGS: We identified and locked an 8-gene assay (CXCL10, FCGR1A, FCGR1B, GBP1, GBP4, IL15, KLRC1, TIMP1) in blood samples from the discovery and derivation phases for discrimination between cases with (N = 49) and without (N = 134) antibody-mediated rejection. In the validation cohort, this 8-gene assay discriminated between cases with (N = 41) and without antibody-mediated rejection (N = 346) with good diagnostic accuracy (ROC AUC 79·9%; 95% CI 72·6 to 87·2, p < 0·0001). The diagnostic accuracy of the 8-gene assay was retained both at time of stable graft function and of graft dysfunction, within the first year and also later after transplantation. The 8-gene assay is correlated with microvascular inflammation and transplant glomerulopathy, but not with the histological lesions of T-cell mediated rejection.INTERPRETATION: We identified and validated a novel 8-gene expression assay that can be used for non-invasive diagnosis of antibody-mediated rejection.FUNDING: The Seventh Framework Programme (FP7) of the European Commission.Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.
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This article is a good source of information and a good way to become familiar with topics such as: Antibody-mediated rejection;Biomarker;Kidney transplantation.

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