ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: SA-OR50

Immune Cell Transcriptome in Living-Donor Kidney Transplant Patients Tolerized With Allogeneic Hematopoietic Stem Cell Transplantation Therapy

Session Information

Category: Transplantation

  • 2002 Transplantation: Clinical

Authors

  • McDaniels, Jennifer M., University of Maryland Baltimore, Baltimore, Maryland, United States
  • Shetty, Amol C., University of Maryland Baltimore, Baltimore, Maryland, United States
  • Rousselle, Thomas, University of Maryland Baltimore, Baltimore, Maryland, United States
  • Leventhal, Joseph, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Ildstad, Suzanne, Talaris Therapeutics Inc, Louisville, Kentucky, United States
  • Mas, Valeria R., University of Maryland Baltimore, Baltimore, Maryland, United States
Background

Long-term outcomes in living donor kidney transplant (LDKT) patients are suboptimal due to lifelong chronic immunosuppression complications. FREEDOM-1 is a randomized, controlled, open-label Phase 3 study of FCR001 in adult LDKT patients. The mechanisms underlying immune tolerance after HSCT are poorly understood. This study deciphered the immune landscape associated with tolerance at single cell resolution.

Methods

Peripheral blood mononuclear cells (PBMCs) from 4 LDKT patients (3 in the FCR001 group and 1 with standard of care (SOC) immunosuppression) were studied at 4 timepoints (T0-, T1-, T3-, and T6-month(s)). Cross-sectional and longitudinal evaluations were done. Analysis was done using CellRanger software and visualized with UMAP. DEGs (FDR≤0.05) identified enriched GO terms and pathways.

Results

Unsupervised PBMCs clustering (>100,000 cells) identified 17 unique cell clusters, including monocytes, natural killer (NK) and T cell subclusters (Fig 1A). At T6, FCR was characterized by decreased NK1, T helper, and T memory cells, while CD14+ monocytes, NK2, and T proliferating cell clusters were increased compared to SOC. A mixed immune cluster was increased in FCR (Fig 1B) and characterized by PD-L1 checkpoint and T cell receptor signaling pathways. There was a higher proportion of cells in S phase from FCR, indicating early alterations in transcriptional activity (Fig 1C). High heterogeneity in NK clusters was observed; NK1 was reduced in FCR (Fig 1D). DEGs showed that NK1 cells were less transcriptionally active in FCR at T6 (Fig 1E).

Conclusion

This study represents the first longitudinal evaluation of PBMCs from LDKT patients underlying mechanisms of tolerance at single cell resolution. Unique patterns of immune cell types, cell states, and transcriptional activity were identified with NK cell subclusters playing a critical role.

Funding

  • Commercial Support