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Abstract: FR-PO787

Molecular and Cellular Landscape of Peripheral Blood Mononuclear Cells (PBMCs) Associated With Kidney Transplantation Operational Tolerance

Session Information

Category: Transplantation

  • 2002 Transplantation: Clinical

Authors

  • Azim, Shafquat, University of Maryland School of Medicine, Baltimore, Maryland, United States
  • Zubair, Haseeb, University of Maryland School of Medicine, Baltimore, Maryland, United States
  • Shetty, Amol C., University of Maryland Baltimore, Baltimore, Maryland, United States
  • McDaniels, Jennifer M., University of Maryland School of Medicine, Baltimore, Maryland, United States
  • Rousselle, Thomas, University of Maryland School of Medicine, Baltimore, Maryland, United States
  • Kuscu, Cem, The University of Tennessee Health Science Center College of Medicine, Memphis, Tennessee, United States
  • Kuscu, Canan, The University of Tennessee Health Science Center College of Medicine, Memphis, Tennessee, United States
  • Talwar, Manish, The University of Tennessee Health Science Center College of Medicine, Memphis, Tennessee, United States
  • Eason, James D., The University of Tennessee Health Science Center College of Medicine, Memphis, Tennessee, United States
  • Maluf, Daniel G., University of Maryland Medical Center, Baltimore, Maryland, United States
  • Mas, Valeria R., University of Maryland School of Medicine, Baltimore, Maryland, United States

Group or Team Name

  • Mas Lab
Background

Under rare event kidney transplant recipient (KTR) establish long-term allograft acceptance without the need of immunosuppressive drugs (ISD), usually due to medical nonadherence. Understanding the immune landscape in patients of spontaneous tolerance can define novel mechanisms of tolerance induction and provide biomarkers for clinical testing to reduce or withdraw ISD.

Methods

PBMCs isolated from non-transplant healthy control (Nor, n=2), KTR on ISD (NwIS, n=3), and KTR with operational tolerance (OT, n=1) were processed for single-cell RNA-seq according to the 10X Genomics Chromium platform and analyzed on CellRanger and Seurat.

Results

Subclusters of T-cell included Treg (FOXP3). Treg was present in higher fraction in NwIS (Fig 1A). Pathway analysis on Treg differentially expressed genes (FDR≤0.05, log2FC≥±1.5) was done using Metascape (Fig 1B). LGALS1 an important effector of Treg-mediated regulation was upregulated specifically in OT. Interestingly, perforin (PRF1), also a mediator of Treg-induced tolerance, was >5-fold less in NwIS compared to N and OT. B cell population was also dissimilar between the three. OT had the highest proportion, while NwIS the lowest. Subclustering B cell identified the presence of a single activated B cell subpopulation in NwIS, which were very low in OT and Nor (Fig 2). However, most of the activated B cells in NwIS were in the G1 phase with decreased CD27 and CD24 expression indicating B cell exhaustion.

Conclusion

Increased LGALS1 and PRF1 in OT indicates a role in achieving tolerance via Tregs. Moreover, abundance in B cell subtypes and associated transcriptome found in OT also indicate tolerance maintenance.

Figure 1: (A) UMAP showing main clusters identified between groups. (B) Pathway analysis using differentially expressed genes between NwIS and Nor.
Figure 2: UMAP of subclustered B-cell population

Funding

  • NIDDK Support