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264 Pearl: pathway exploration and analysis in renal disease in the accelerating medicine partnership (amp) lupus network
  1. CC Berthier1,
  2. DA Rao2,
  3. A Arazi3,
  4. EP Browne3,
  5. T Eisenhaure3,
  6. N Hacohen3,
  7. D Lieb3,
  8. B Diamond4 and
  9. M Kretzler1
  1. 1University of Michigan, Internal Medicine, Ann Arbour, USA
  2. 2Brigham and Women’s Hospital, Rheumatology, Boston, USA
  3. 3Broad Institute, N/A, Cambridge, USA
  4. 4Feinstein Institute for Medical Research, Centre for Autoimmunity and Musculoskeletal Diseases, Manhasset, USA

Abstract

Background and aims 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. Our goal is to demonstrate the feasibility of single cell and low-input transcriptomic analyses of LN kidney and urine cells.

Methods Cells from urine and renal biopsies performed for clinical diagnosis from inform-consented patients (1 class III, 3 class IV+V, 1 class V) and 1 control (healthy part of tumour nephrectomy) were isolated, frozen, sorted and analysed by RNAseq.

Results Bulk flow sorted cell populations (CD45, epithelial) from kidney samples can separate LN from controls based on gene expression. IFN stimulated genes were differentially expressed in renal CD45 LN cells. Analysis of single cells sorted from 4 LN kidney biopsies revealed major differences in infiltrates composition, with 2 samples demonstrating a high percentage of B cells (average of 18% compared to no B cells in the other 2 samples) and CD4 T cells (18% vs 8%), and low percentage of CD8 T cells (9% vs 23%). A high transcriptomic lupus interferon signature was detected in urine CD45 cells. Distinct infiltrates and distinct expression profiles were detected across patients.

Conclusions The PEARL-Phase 0 project shows the feasibility of single cell isolation and transcriptomic analysis from LN kidney and urine. Analyses at a bigger scale in the two next phases of the project will accelerate discovery of new therapeutic targets and identification of biomarkers to guide therapeutic decisions in lupus nephritis and integrate the treatment effect.

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