Kidney Week

Abstract: FR-OR127

Deciphering Shared Gene Expression Patterns by Whole-Genome Transcriptomics of Urinary Cells and Kidney Allograft Biopsies

Session Information

• Transplantation: Basic Research
  November 08, 2019 | Location: 150, Walter E. Washington Convention Center
  Abstract Time: 05:42 PM - 05:54 PM

Category: Transplantation

• 1901 Transplantation: Basic

Authors

• Lubetzky, Michelle L., Weill Cornell Medical College, New York, New York, United States

Michelle L. Lubetzky, MD, FASN



Dr. Michelle Lubetzky is an Assistant Professor of Medicine at Weill Cornell Medical College and an Assistant Attending Physician at NewYork-Presbyterian Hospital/Weill Cornell Medical Center. She received her MD at the Albert Einstein College of Medicine. She completed her residency and fellowships at NewYork-Presbyterian Hospital/Weill Cornell Medical Center. My research focuses on the development of urine biomarkers to predict kidney-transplant related complications including conducting human translational studies in the field of kidney transplantation.

• Muthukumar, Thangamani, Weill Cornell Medical College, New York, New York, United States

Thangamani Muthukumar,

• Lee, John Richard, Weill Cornell Medical College, New York, New York, United States

John Richard Lee,

• Dadhania, Darshana, Weill Cornell Medical College, New York, New York, United States

Darshana Dadhania,

• Cassidy, Michael F., Weill Cornell Medicine, New York, New York, United States

Michael F. Cassidy,

• Seshan, Surya V., Weill Cornell Medical Center, New York, New York, United States

Surya V. Seshan,

• Salvatore, Steven, Weill Cornell Medical College, New York, New York, United States

Steven Salvatore,

• Suthanthiran, Manikkam, Weill Cornell Medical College, New York, New York, United States

Manikkam Suthanthiran,

Background

Urinary cell mRNA profiling to interrogate kidney allograft (KTx) status is based on the premise that the allograft can function as an in-vivo flow cytometer and sort graft destructive/protective T cells into the urinary space. We used RNA-Seq of urinary cells to demonstrate that urinary cell mRNA profiles mirror intragraft events and urinary cells are enriched for immune cells in acute rejection

Methods

We performed global RNA-seq to characterize mRNA transcriptomes of urinary cells from 57 KTx recipients with T Cell Mediated Rejection (TCMR), n=22, Antibody Mediated Rejection (AMR), n=8, Normal, n=27, and allograft tissues from 49 KTx recipients (ACR n=12, AMR n=17, and Normal n=20). We analyzed the urine and biopsy profiles using Gene Set Enrichment Analysis (GSEA) and a gene-signature expression based cell-type deconvolution tool xCell.

Results

By GSEA analysis, genes upregulated in the KTx biopsies with TCMR and AMR were upregulated in the urinary cells with TCMR and AMR (FDR-P<0.01). There were 76 differentially expressed mRNAs that were shared between urine and biopsy profiles in TCMR, and 191 differentially expressed mRNAs that were shared between urine and biosy AMR. Deconvolution analysis revealed higher enrichment of stromal cell score in the biopsies compared to urine, whereas immune cell types were enriched in the urine.

Conclusion

GSEA of RNA-seq data from urinary cells and kidney allografts demonstrate enrichment of genes related to immune cells in urine that is undiluted by the stromal component. Our data support the use of urine as an excellent biospecimen for biomarker discovery and development as well as for deciphering the anti-allograft repertory.

(Figure 1, Panel A: GSEA, Panel B: Venn Diagram Shared Genes, Panel C&D: xCell immune cell types in TCMR and AMR, Blue=Biopsy and Yellow=urine)