Abstract: FR-PO767
Natural Killer Cell Activity Is Increased in Chronic Active Antibody-Mediated Rejection (caABMR) of Human Kidney Allografts
Session Information
- Transplantation: Clinical - Biomarkers
November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Transplantation
- 2002 Transplantation: Clinical
Authors
- Rahim, Shab E Gul, Weill Cornell Medicine, New York, New York, United States
- Varma, Elly, Weill Cornell Medicine, New York, New York, United States
- Salinas, Thalia, Weill Cornell Medicine, New York, New York, United States
- Li, Carol Y., Weill Cornell Medicine, New York, New York, United States
- Snopkowski, Catherine, Weill Cornell Medicine, New York, New York, United States
- Salvatore, Steven, Weill Cornell Medicine, New York, New York, United States
- Seshan, Surya V., Weill Cornell Medicine, New York, New York, United States
- Dadhania, Darshana M., 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
caABMR of the kidney allograft has several unique clinicopathological features that are distinct from acute ABMR. Using RNA sequencing of kidney allograft biopsies, we tested the hypothesis that caABMR is characterized by heightened natural killer (NK) cell activity.
Methods
We studied 57 biopsies from 57 adult kidney transplant recipients; 18 surveillance biopsies reported as No Rejection (normal) and 39 for-cause biopsies reported as caABMR (N=15), acute ABMR (N=7), and TCMR (N=17). Biopsies were independently assessed by two transplant pathologists using immunofluorescence, light, and electron microscopy. Individual cDNA libraries were prepared from each RNA sample, pooled, and sequenced on an Illumina sequencer. All quality measures were met. Standard tools were used for bioinformatic analysis.
Results
There were 1425 upregulated and 29 downregulated genes that were different (two-fold difference and P-FDR<0.05) between caABMR and No Rejection biopsies. Among the 391 highly overexpressed genes (four-fold difference and P-FDR<0.05) between caABMR and No rejection, 60 were specific for caABMR (Fig 1A). Cell-type annotation of these 60 genes revealed an increase in NK cells (Fig 1B). Several genes involved in the NK cell-mediated cytotoxicity pathway were upregulated in caABMR. Deconvolution analysis revealed an increased proportion of NK cells in caABMR (Fig 1C). Gene set variation analysis score for the NK cell cytotoxicity pathway set of 133 genes was highest for caABMR (Figure 1D). In addition, tissue expression of the terminal complement protein C9 was increased in acute AMBR but not in caABMR compared to No Rejection.
Conclusion
Our findings of heightened NK cell activity in caABMR suggest that the antibody-dependent cellular cytotoxicity pathway mediated by NK cells likely plays a major in mediating tissue injury in caABMR.