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Abstract: FR-PO726

Molecular Similarity Between Chronic Active Antibody-Mediated Rejection (CA-ABMR) and Acute T Cell-Mediated Rejection (TCMR) of Human Kidney Allografts

Session Information

  • Transplantation: Basic
    November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Transplantation

  • 2101 Transplantation: Basic

Authors

  • Shah, Yajas, Weill Cornell Medicine, New York, New York, United States
  • Li, Carol Y., Weill Cornell Medicine, New York, New York, United States
  • Wright, Sheavonnie, Weill Cornell Medicine, New York, New York, United States
  • Devito, Alex, Weill Cornell Medicine, New York, New York, United States
  • Salinas, Thalia, Weill Cornell Medicine, New York, New York, United States
  • Salvatore, Steven, Weill Cornell Medicine, New York, New York, United States
  • Sawinski, Deirdre L., Weill Cornell Medicine, New York, New York, United States
  • Dadhania, Darshana M., Weill Cornell Medicine, New York, New York, United States
  • Seshan, Surya V., Weill Cornell Medicine, New York, New York, United States
  • Suthanthiran, Manikkam, Weill Cornell Medicine, New York, New York, United States
  • Muthukumar, Thangamani, Weill Cornell Medicine, New York, New York, United States
Background

CA-ABMR, even without concomitant histological TCMR, is characterized by an increased abundance of NK Cells and T cells. We RNA-sequenced kidney allograft biopsies to test the hypothesis that CA-ABMR, but not active-ABMR, is exemplified by the overexpression of key gene sets that are similar to TCMR.

Methods

We did RNA-seq of 57 biopsies from 57 kidney transplant recipients; 39 for-cause biopsies (15 CA-ABMR, 17 TCMR, & 7 active-ABMR), and 18 surveillance biopsies (no rejection [NR]). All biopsies were evaluated independently by two transplant pathologists. We isolated total RNA from stored biopsy samples, prepared cDNA libraries, and sequenced pooled libraries on an Illumina sequencer. After appropriate quality checks, we used standard bioinformatic tools for data analysis.

Results

There were 1425 genes increased and 29 reduced between CA-ABMR and NR biopsies (FC≥2 & P-FDR<0.05); 1829 were increased and 164 were reduced between TCMR and NR biopsies. T and NK cells were the top cell types and pathways in CA-ABMR and TCMR (Fig.1).

Differential gene expression analysis between CA-ABMR and TCMR biopsies yielded only one gene, MARCHF4, that was significantly different. Cellular deconvolution revealed a similar proportion of immune cells in the three rejection categories; principal component analysis of deconvolved immune cell transcriptomes separated CA-ABMR and TCMR from active-ABMR and NR biopsies (Fig.2).

Conclusion

CA-ABMR exhibits an immune transcriptome profile that resembles TCMR biopsies. Our findings, besides advancing our knowledge of the pathogenesis of CA-ABMR, provide a compelling argument for the pharmacological targeting of T cells and NK cells in CA-ABMR.

Funding

  • Other NIH Support