Antibody Mediated Rejection and T-cell Mediated Rejection Molecular Signatures Using Next-Generation Sequencing in Kidney Transplant Biopsies
Cortes Garcia, Esteban (Paris Institute for Transplantation and Organ Regeneration)
Giarraputo, Alessia (Paris Institute for Transplantation and Organ Regeneration. INSERM U970. Université Paris Cité)
Racapé, Maud (Paris Institute for Transplantation and Organ Regeneration)
Goutaudier, Valentin (Paris Institute for Transplantation and Organ Regeneration)
Ursule-Dufait, Cindy (Paris Institute for Transplantation and Organ Regeneration)
de la Grange, Pierre (GenoSplice)
Adoux, Lucie (Institut Cochin. INSERM. Centre National de la Recherche Scientifique (CNRS). Université Paris Cité)
Raynaud, Marc (Paris Institute for Transplantation and Organ Regeneration)
Couderau, Clément (Paris Institute for Transplantation and Organ Regeneration)
Mezine, Fariza (Paris Institute for Transplantation and Organ Regeneration)
Dagobert, Jessie (Paris Institute for Transplantation and Organ Regeneration. INSERM U970. Université Paris Cité)
Bestard, Oriol (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Moreso, Francesc (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Villard, Jean (Geneva University Hospitals. Department of Diagnostic. Transplantation Immunology Unit and National Reference Laboratory for Histocompatibility)
Halleck, Fabian (Charité-Universitätsmedizin Berlin)
Giral, Magali (CRT2I-Center for Research in Transplantation and Translational Immunology. INSERM. Nantes Université)
Brouard, Sophie (CRT2I-Center for Research in Transplantation and Translational Immunology. INSERM. Nantes Université)
Danger, Richard (CRT2I-Center for Research in Transplantation and Translational Immunology. INSERM. Nantes Université)
Gourraud, Pierre-Antoine (CHU de Nantes)
Rabant, Marion (Université Paris Cité. Assistance Publique - Hôpitaux de Paris. Necker-Enfants Malades Hospital. Department of Pathology)
Couzi, Lionel (Centre Hospitalier Universitaire de Bordeaux)
Le Quintrec, Moglie (Centre Hospitalier Universitaire de Montpellier. Department of Nephrology Dialysis and Kidney Transplantation)
Kamar, Nassim (Toulouse Rangueil University Hospital. Department of Nephrology and Organ Transplantation)
Morelon, Emmanuel (Hospices Civils de Lyon)
Vrtovsnik, François (Assistance Publique-Hôpitaux de Paris (APHP). Bichat Hospital)
Taupin, Jean-Luc (Hôpital Saint-Louis (París, França))
Snanoudj, Renaud (Hôpital de Bicêtre. Université Paris-Saclay)
Legendre, Christophe (Necker Hospital)
Anglicheau, Dany (Necker Hospital)
Budde, K (Charité-Universitätsmedizin Berlin)
Lefaucheur, Carmen (Saint-Louis Hospital)
Loupy, Alexandre (Necker Hospital)
Aubert, Olivier (Necker Hospital)
Universitat Autònoma de Barcelona. Departament de Medicina

Date:	2024
Abstract:	Recently, interest in transcriptomic assessment of kidney biopsies has been growing. This study investigates the use of NGS to identify gene expression changes and analyse the pathways involved in rejection. An Illumina bulk RNA sequencing on the polyadenylated RNA of 770 kidney biopsies was conducted. Differentially-expressed genes (DEGs) were determined for AMR and TCMR using DESeq2. Genes were segregated according to their previous descriptions in known panels (microarray or the Banff Human Organ Transplant (B-HOT) panel) to obtain NGS-specific genes. Pathway enrichment analysis was performed using the Reactome and Kyoto Encyclopaedia of Genes and Genomes (KEGG) public repositories. The differential gene expression using NGS analysis identified 6,141 and 8,478 transcripts associated with AMR and TCMR. While most of the genes identified were included in the microarray and the B-HOT panels, NGS analysis identified 603 (9. 8%) and 1,186 (14%) new specific genes. Pathways analysis showed that the B-HOT panel was associated with the main immunological processes involved during AMR and TCMR. The microarrays specifically integrated metabolic functions and cell cycle progression processes. Novel NGS-specific based transcripts associated with AMR and TCMR were discovered, which might represent a novel source of targets for drug designing and repurposing.
Grants:	European Commission 754995
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Next generation sequencing ; RNA-seq experiment ; Kidney biopsies ; Molecular signature ; Allograft rejection ; Kidney transplantation
Published in:	Transplant International, Vol. 37 (july 2024) , ISSN 1432-2277

DOI: 10.3389/ti.2024.13043
PMID: 39050190

12 p, 3.0 MB

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