Antibody Mediated Rejection and T-cell Mediated Rejection Molecular Signatures Using Next-Generation Sequencing in Kidney Transplant Biopsies

Abstract

Kidney biopsies; Kidney transplantation; Next generation sequencing

Biopsias de riñón; Trasplante de riñón; Secuenciación de nueva generación

Biòpsies de ronyó; Trasplantament de ronyó; Seqüenciació de nova generació

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.

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. The EU-TRAIN study was funded by the European Union’s Horizon 2020 research and innovation program under grant agreement no. 754995. The KTD-Innov study was funded by the French government, with financial support managed by the National Research Agency (ANR) under the program “Investissements d’avenir,” with the grant agreement no. ANR-17-RHUS-0010. INSERM-Action thématique incitative sur programme Avenir (ATIP-Avenir) provided financial support.