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Immune Cell Phenotype of Acute Rejection of Pancreas Allografts by RNA Sequencing Analysis

C. Hughes, H. Yang, C. Snopkowski, C. Li, D. M. Dadhania, S. Sultan, C. Hartono, M. Suthanthiran, S. V. Seshan, T. Muthukumar

Weill Cornell Medicine, New York, NY

Meeting: 2022 American Transplant Congress

Abstract number: 434

Keywords: Gene expression, Pancreas transplantation, Rejection

Topic: Clinical Science » Pancreas » 65 - Pancreas and Islet: All Topics

Session Information

Session Name: Pancreas and Islet: All Topics

Session Type: Rapid Fire Oral Abstract

Date: Tuesday, June 7, 2022

Session Time: 3:30pm-5:00pm

 Presentation Time: 4:40pm-4:50pm

Location: Hynes Room 210

*Purpose: Long term survival of pancreas allografts are inferior to kidney allografts. Molecular mechanisms underpinning pancreas allograft rejection and failure have not been explored in detail. Decoding the immune cell phenotype of acute rejection (AR) of pancreatic allografts may help better understand the mechanism of pancreas allograft failure and develop effective therapeutic strategies.

*Methods: We did RNA-sequencing and data analysis of 10 pancreas allograft biopsies, obtained from 10 recipients; 4 biopsies were categorized as acute T cell mediated rejection (ACMR), 2 biopsies as acute antibody mediated rejection (AMR), and 4 biopsies as normal/non-specific (Normal), as per the Banff 2011 classification of pancreas allograft pathology. RNA was isolated from tissue specimens stored in RNAlater and were sequenced on an Illumina sequencer. After QC check of the RNA-seq data, we quantified the expression of transcripts using Salmon. Non-normalized transcript counts were used as input to DESeq2 to perform differential expression analysis. Ingenuity Pathway Analysis was run using the differential expression output to identify biological pathways of interest. We used xCell to discover cell type enrichment in the whole RNA-seq dataset.

*Results: We identified 231 differentially expressed genes (FDR < 0.05, log2 fold change >1) between AR and Normal; 212 were upregulated and 19 were downregulated in AR (Figure 1).

Figure 1. Volcano plot showing the log2 fold change and -log p-value of differentially expressed genes between rejection and normal.

Innate and adaptive immune system molecular pathways were enriched in AR. Figure 2 depicts the cell types enriched in AR and Normal.

Figure 2. Boxplots showing xCell enrichment scores in pancreas allografts

*Conclusions: Our unbiased characterization of the mRNA transcriptome of pancreas allograft has decoded the complex immune cell phenotype of acute rejection and normal. Our preliminary findings will be further explored to better understand the molecular mechanisms of pancreas rejection.

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To cite this abstract in AMA style:

Hughes C, Yang H, Snopkowski C, Li C, Dadhania DM, Sultan S, Hartono C, Suthanthiran M, Seshan SV, Muthukumar T. Immune Cell Phenotype of Acute Rejection of Pancreas Allografts by RNA Sequencing Analysis [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/immune-cell-phenotype-of-acute-rejection-of-pancreas-allografts-by-rna-sequencing-analysis/. Accessed May 11, 2025.

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