Abstract: FR-PO694

Update about PEARL: Pathway Exploration and Analysis in Renal Disease in the Accelerating Medicine Partnership (AMP) Lupus Network

Session Information

Category: Glomerular

  • 1001 Glomerular: Basic/Experimental Immunology and Inflammation

Authors

  • Berthier, Celine C., University of Michigan, Ann Arbor, Michigan, United States
  • Arazi, Arnon, Broad Institute, Cambridge, Massachusetts, United States
  • Rao, Deepak, Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Eisenhaure, Thomas, Broad Institute, Cambridge, Massachusetts, United States
  • Hacohen, Nir, Broad Institute, Cambridge, Massachusetts, United States
  • Lieb, David J., Broad Institute, Cambridge, Massachusetts, United States
  • Diamond, Betty, The Feinstein Institute for Medical Research, Manhasset, New York, United States
  • Kretzler, Matthias, University of Michigan, Ann Arbor, Michigan, United States

Group or Team Name

  • PEARL team members
Background

Despite treatments, a substantial proportion of lupus nephritis (LN) patients progress to end stage renal disease and death. Detailed transcriptomic analyses of LN kidneys may identify new therapeutic targets. The AMP-PEARL Phase 1 project is to identify renal and urine LN single cell signatures.

Methods

Cells from urine and renal biopsies performed for clinical diagnosis from inform-consented patients (26 LN, 10 healthy controls) were isolated, frozen into Cryostor solution, sorted and profiled by RNAseq.

Results

A total of 15 immune cell populations active in the inflamed kidney were identified and revealed significant differences in subset frequencies across LN patients (e.g. B-cells, dendritic cells). Genes expression in cells from LN patients compared to those in healthy controls highlighted unique LN dysregulated genes/pathways (such as the expected IFN). The renal and urine signatures significantly correlated, suggesting that urine cells could be used as potential markers for longitudinal monitoring and assessment of kidney inflammation. Two chemokine receptors (CXCR4 and CX3CR1) were expressed on the surface of almost all infiltrating immune cells which may be new therapeutic targets.

Conclusion

Preliminary results from the AMP-PEARL-Phase 1 study identified LN active cells and pathways, that can be used to guide the development of novel therapies. Analyses at a bigger scale in the phase 2 of the project will accelerate discovery of new therapeutic targets and identification of biomarkers to guide therapeutic decisions in LN and integrate the treatment effect.

Funding

  • Other NIH Support