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

EBioMedicine
Elisabet Van LoonMaarten Naesens

Abstract

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. 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. 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 antibo...Continue Reading

Citations

Jul 31, 2019·Transplant International : Official Journal of the European Society for Organ Transplantation·Caroline WehmeierStefan Schaub
Dec 14, 2019·Current Opinion in Organ Transplantation·Ondrej ViklickyPetra Hruba
Mar 27, 2020·Journal of Clinical Medicine·Julie De Beule, Ina Jochmans
Jul 1, 2020·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Elisabet Van LoonMaarten Naesens
Aug 6, 2020·International Journal of Molecular Sciences·Marco QuagliaVincenzo Cantaluppi
Sep 28, 2020·Transplant International : Official Journal of the European Society for Organ Transplantation·Veerle P W M WijtvlietKristien J Ledeganck
Mar 10, 2020·Transplantation·Malou L H SnijdersMarian C Clahsen-van Groningen
Apr 30, 2021·Néphrologie & thérapeutique·Elisabet Van Loon, Maarten Naesens
May 22, 2021·Frontiers in Molecular Biosciences·Yicun WangXiaopeng Hu
Nov 17, 2020·Transplantation·Edward John Filippone, John L Farber

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Datasets Mentioned

BETA
GSE
129166

Methods Mentioned

BETA
biopsies
biopsy

Clinical Trials Mentioned

NCT02832661

Software Mentioned

biosigner R
SAS
GraphPad
GraphPad Prism
Scopus
ROC CONTRAST
BIOMARGIN
R

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