Development and validation of a peripheral blood mRNA assay for the assessment of antibody-mediated kidney allograft rejection: A multicentre, prospective study
| Autor: | Maarten Coemans, Ben Sprangers, Marie Essig, Laure-Hélène Noël, Saleh Yazdani, Leentje Van Lommel, Stéphane Gazut, Henriette de Loor, Frans Schuit, Evelyne Lerut, Wilfried Gwinner, Dany Anglicheau, Maarten Naesens, Pierre Marquet, Dirk Kuypers, Elisabet Van Loon, Lieven Thorrez |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
Graft Rejection Male 0301 basic medicine Oncology medicine.medical_specialty Research paper Antibodies General Biochemistry Genetics and Molecular Biology Kidney transplantation 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Clinical endpoint Humans Transplantation Homologous Prospective Studies RNA Messenger Derivation Prospective cohort study Kidney biology business.industry Liquid Biopsy Reproducibility of Results Biomarker General Medicine Middle Aged Prognosis medicine.disease Kidney Transplantation 030104 developmental biology medicine.anatomical_structure ROC Curve Allograft rejection Antibody-mediated rejection 030220 oncology & carcinogenesis biology.protein Biomarker (medicine) Female Antibody business Cell-Free Nucleic Acids Biomarkers |
| Zdroj: | EBioMedicine |
| ISSN: | 2352-3964 |
| DOI: | 10.1016/j.ebiom.2019.07.028 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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