Transplant International (Jul 2024)
Antibody Mediated Rejection and T-cell Mediated Rejection Molecular Signatures Using Next-Generation Sequencing in Kidney Transplant Biopsies
- Esteban Cortes Garcia,
- Alessia Giarraputo,
- Maud Racapé,
- Valentin Goutaudier,
- Cindy Ursule-Dufait,
- Pierre de la Grange,
- Lucie Adoux,
- Marc Raynaud,
- Clément Couderau,
- Fariza Mezine,
- Jessie Dagobert,
- Oriol Bestard,
- Francesc Moreso,
- Jean Villard,
- Fabian Halleck,
- Magali Giral,
- Sophie Brouard,
- Richard Danger,
- Pierre-Antoine Gourraud,
- Marion Rabant,
- Lionel Couzi,
- Moglie Le Quintrec,
- Nassim Kamar,
- Emmanuel Morelon,
- François Vrtovsnik,
- Jean-Luc Taupin,
- Renaud Snanoudj,
- Christophe Legendre,
- Christophe Legendre,
- Dany Anglicheau,
- Dany Anglicheau,
- Klemens Budde,
- Carmen Lefaucheur,
- Carmen Lefaucheur,
- Alexandre Loupy,
- Alexandre Loupy,
- Olivier Aubert,
- Olivier Aubert
Affiliations
- Esteban Cortes Garcia
- Université Paris Cité, INSERM U970, Paris Institute for Transplantation and Organ Regeneration, Paris, France
- Alessia Giarraputo
- Université Paris Cité, INSERM U970, Paris Institute for Transplantation and Organ Regeneration, Paris, France
- Maud Racapé
- Université Paris Cité, INSERM U970, Paris Institute for Transplantation and Organ Regeneration, Paris, France
- Valentin Goutaudier
- Université Paris Cité, INSERM U970, Paris Institute for Transplantation and Organ Regeneration, Paris, France
- Cindy Ursule-Dufait
- Université Paris Cité, INSERM U970, Paris Institute for Transplantation and Organ Regeneration, Paris, France
- Pierre de la Grange
- GenoSplice, Paris, France
- Lucie Adoux
- Université Paris Cité, Centre National de la Recherche Scientifique (CNRS), INSERM, Institut Cochin, Paris, France
- Marc Raynaud
- Université Paris Cité, INSERM U970, Paris Institute for Transplantation and Organ Regeneration, Paris, France
- Clément Couderau
- Université Paris Cité, INSERM U970, Paris Institute for Transplantation and Organ Regeneration, Paris, France
- Fariza Mezine
- Université Paris Cité, INSERM U970, Paris Institute for Transplantation and Organ Regeneration, Paris, France
- Jessie Dagobert
- Université Paris Cité, INSERM U970, Paris Institute for Transplantation and Organ Regeneration, Paris, France
- Oriol Bestard
- Department of Nephrology and Kidney Transplantation, Vall d'Hebron Hospital Universitari, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain
- Francesc Moreso
- Department of Nephrology and Kidney Transplantation, Vall d'Hebron Hospital Universitari, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain
- Jean Villard
- Transplantation Immunology Unit and National Reference Laboratory for Histocompatibility, Department of Diagnostic, Geneva University Hospitals, Geneva, Switzerland
- Fabian Halleck
- Department of Nephrology and Intensive Care, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- Magali Giral
- Nantes Université, INSERM, CRT2I-Center for Research in Transplantation and Translational Immunology, Nantes, France
- Sophie Brouard
- Nantes Université, INSERM, CRT2I-Center for Research in Transplantation and Translational Immunology, Nantes, France
- Richard Danger
- Nantes Université, INSERM, CRT2I-Center for Research in Transplantation and Translational Immunology, Nantes, France
- Pierre-Antoine Gourraud
- Nantes Université, Centre Hospitalier Universitaire de Nantes, Pôle Hospitalo-Universitaire 11: Santé Publique, Clinique des données, INSERM, Centre d’Investigation Clinique 1413, Nantes, France
- Marion Rabant
- Department of Pathology, Necker-Enfants Malades Hospital, Assistance Publique - Hôpitaux de Paris, Université Paris Cité, Paris, France
- Lionel Couzi
- 0Centre Hospitalier Universitaire de Bordeaux, Service de Néphrologie, Transplantation, Dialyse et Aphérèses, Bordeaux, France
- Moglie Le Quintrec
- 1Department of Nephrology Dialysis and Kidney Transplantation, Centre Hospitalier Universitaire de Montpellier, Montpellier, France
- Nassim Kamar
- 2Department of Nephrology and Organ Transplantation, Toulouse Rangueil University Hospital, INSERM UMR 1291, Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), University Paul Sabatier, Toulouse, France
- Emmanuel Morelon
- 3Department of Transplantation, Nephrology and Clinical Immunology, Hospices Civils de Lyon, Lyon, France
- François Vrtovsnik
- 4Department of Kidney Transplantation, Bichat Hospital, Assistance Publique—Hôpitaux de Paris (APHP), Paris, France
- Jean-Luc Taupin
- 5Laboratory of Immunology and Histocompatibility, Hôpital Saint-Louis Assistance Publique - Hôpitaux de Paris, Paris, France
- Renaud Snanoudj
- 6Assistance Publique des Hôpitaux de Paris (AP-HP), Université Paris-Saclay, Hôpital de Bicêtre, Service de Néphrologie et Transplantation, Le Kremlin-Bicêtre, France
- Christophe Legendre
- Université Paris Cité, INSERM U970, Paris Institute for Transplantation and Organ Regeneration, Paris, France
- Christophe Legendre
- 7Department of Kidney Transplantation, Necker Hospital, Assistance Publique—Hôpitaux de Paris, Paris, France
- Dany Anglicheau
- Université Paris Cité, INSERM U970, Paris Institute for Transplantation and Organ Regeneration, Paris, France
- Dany Anglicheau
- 7Department of Kidney Transplantation, Necker Hospital, Assistance Publique—Hôpitaux de Paris, Paris, France
- Klemens Budde
- Department of Nephrology and Intensive Care, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- Carmen Lefaucheur
- Université Paris Cité, INSERM U970, Paris Institute for Transplantation and Organ Regeneration, Paris, France
- Carmen Lefaucheur
- 8Kidney Transplant Department, Saint-Louis Hospital, Assistance Publique—Hôpitaux de Paris, Paris, France
- Alexandre Loupy
- Université Paris Cité, INSERM U970, Paris Institute for Transplantation and Organ Regeneration, Paris, France
- Alexandre Loupy
- 7Department of Kidney Transplantation, Necker Hospital, Assistance Publique—Hôpitaux de Paris, Paris, France
- Olivier Aubert
- Université Paris Cité, INSERM U970, Paris Institute for Transplantation and Organ Regeneration, Paris, France
- Olivier Aubert
- 7Department of Kidney Transplantation, Necker Hospital, Assistance Publique—Hôpitaux de Paris, Paris, France
- DOI
- https://doi.org/10.3389/ti.2024.13043
- Journal volume & issue
-
Vol. 37
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.
Keywords
- next generation sequencing
- RNA-seq experiment
- kidney biopsies
- molecular signature
- allograft rejection
- kidney transplantation
