Integrative Analyses of Circulating Small Rnas and Paired Kidney Graft Transcriptome in Transplant Glomerulopathy

C. Kuscu¹, K. Manjari², M. Akram³, C. Kuscu⁴, A. Wolen,⁴, A. Bajwa⁴, J. Eason⁴, D. G. Maluf⁵, V. Mas⁶, E. Akalin⁷

¹Surgery, James D Eason Transplant Institute, UTHSC, Memphis, TN, ²Department of Systems and Computational Biology, School of Life Sciences, University of Hyderabad,, Hyderabad,, India, ³Center for Biomedical Informatics, University of Tennessee Health Science Center, Memphis, TN, ⁴Surgery, James D Eason Transplant Institute, Memphis, TN, ⁵Surgery, Program in Transplantation, University of Maryland, Baltimore, MD, ⁶Surgery, Division Surgical Science, University of Maryland, Baltimore, MD, ⁷Medicine, Montefiore Medical Center, Abdominal Transplant Program, Albert Einstein College of Medicine,, NYC, NY

Meeting: 2021 American Transplant Congress

Abstract number: 15

Keywords: Gene expression, Genomic markers, Kidney transplantation, Recurrence

Topic: Clinical Science » Biomarkers, Immune Assessment and Clinical Outcomes

Session Information

Session Name: Biomarkers, Immune Assessment and Clinical Outcomes - I

Session Type: Rapid Fire Oral Abstract

Date: Saturday, June 5, 2021

Session Time: 4:30pm-5:30pm

Presentation Time: 4:50pm-4:55pm

Location: Virtual

*Purpose: Transplant glomerulopathy (TG) develops through multiple mechanisms including donor-specific antibodies, T cells and innate immunity. We investigate the role of circulating small RNAs (sRNAs) in TG comparing intragraft gene expression profiles.

*Methods: sRNAs profiles were evaluated in serum of kidney transplant recipients with biopsy-proven TG and normal allograft function using RNA sequencing. An integrative approach was applied to link miRNA changes in serum with gene expression profiles from the paired allograft samples.

*Results: Among total sRNA population, miRNAs were the most abundant species, compromising approximately 30% of total sRNAs in the serum of kidney transplant patients (Fig. A). Fragments arising from mature tRNA and rRNA were also detected. Most of tRNA fragments (tRFs) were generated from 5’ ends of mature tRNA and mainly from two parental tRNAs: tRNA-Gly and tRNA-Glu (Fig. B). Paired gene expression analysis from allograft tissues showed changes in canonical pathways related to immune activation such as iCos-iCosL signaling pathway in T helper cells, Th1 and Th2 activation pathway, and dendritic cell maturation (Fig. C, D). mRNA targets of down regulated miRNAs such as miR-1224-5p, miR-4508, miR-320, miR-378a from serum were globally upregulated in tissue.

*Conclusions: This is the first study to report the circulating sRNA profiles in transplant patients with TG using next generation sequencing. A novel circulating tRNA fragment TG signature is reported. Integration of sRNA profiles from serum with gene expression from tissues showed that changes in serum miRNAs support the role of T-cell mediated mechanisms in ongoing allograft injury.

To cite this abstract in AMA style:

Kuscu C, Manjari K, Akram M, Kuscu C, Wolen A, Bajwa A, Eason J, Maluf DG, Mas V, Akalin E. Integrative Analyses of Circulating Small Rnas and Paired Kidney Graft Transcriptome in Transplant Glomerulopathy [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/integrative-analyses-of-circulating-small-rnas-and-paired-kidney-graft-transcriptome-in-transplant-glomerulopathy/. Accessed November 21, 2024.

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