Urinary cell transcriptomics and acute rejection in human kidney allografts.

TitleUrinary cell transcriptomics and acute rejection in human kidney allografts.
Publication TypeJournal Article
Year of Publication2020
AuthorsVerma A, Muthukumar T, Yang H, Lubetzky M, Cassidy MF, Lee JR, Dadhania DM, Snopkowski C, Shankaranarayanan D, Salvatore SP, Sharma VK, Xiang JZ, De Vlaminck I, Seshan SV, Mueller FB, Suhre K, Elemento O, Suthanthiran M
JournalJCI Insight
Date Published2020 Feb 27

BACKGROUNDRNA sequencing (RNA-Seq) is a molecular tool to analyze global transcriptional changes, deduce pathogenic mechanisms, and discover biomarkers. We performed RNA-Seq to investigate gene expression and biological pathways in urinary cells and kidney allograft biopsies during an acute rejection episode and to determine whether urinary cell gene expression patterns are enriched for biopsy transcriptional profiles.METHODSWe performed RNA-Seq of 57 urine samples collected from 53 kidney allograft recipients (patients) with biopsies classified as acute T cell-mediated rejection (TCMR; n = 22), antibody-mediated rejection (AMR; n = 8), or normal/nonspecific changes (No Rejection; n = 27). We also performed RNA-Seq of 49 kidney allograft biopsies from 49 recipients with biopsies classified as TCMR (n = 12), AMR (n = 17), or No Rejection (n = 20). We analyzed RNA-Seq data for differential gene expression, biological pathways, and gene set enrichment across diagnoses and across biospecimens.RESULTSWe identified unique and shared gene signatures associated with biological pathways during an episode of TCMR or AMR compared with No Rejection. Gene Set Enrichment Analysis demonstrated enrichment for TCMR biopsy signature and AMR biopsy signature in TCMR urine and AMR urine, irrespective of whether the biopsy and urine were from the same or different patients. Cell type enrichment analysis revealed a diverse cellular landscape with an enrichment of immune cell types in urinary cells compared with biopsies.CONCLUSIONSRNA-Seq of urinary cells and biopsies, in addition to identifying enriched gene signatures and pathways associated with TCMR or AMR, revealed genomic changes between TCMR and AMR, as well as between allograft biopsies and urinary cells.

Alternate JournalJCI Insight
PubMed ID32102984
PubMed Central IDPMC7101135
Grant ListR37 AI051652 / AI / NIAID NIH HHS / United States
R01 CA194547 / CA / NCI NIH HHS / United States
UL1 TR002384 / TR / NCATS NIH HHS / United States
UL1 TR000457 / TR / NCATS NIH HHS / United States
K08 DK087824 / DK / NIDDK NIH HHS / United States