Molecular architecture of proliferative lupus nephritis as elucidated using 50-plex imaging mass cytometry proteomics

Anto Sam Crosslee Louis Sam Titus, Ying Tan, Phuongthy Tran, Julius Lindblom, Maryann Ivbievbiokun, Yitian Xu, Junjun Zheng, Ioannis Parodis, Qi Cai, Anthony Chang, Shu Hsia Chen, Minghui Zhao, Chandra Mohan

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Due to unique advantages that allow high-dimensional tissue profiling, we postulated imaging mass cytometry (IMC) may shed novel insights on the molecular makeup of proliferative lupus nephritis (LN). This study interrogates the spatial expression profiles of 50 target proteins in LN and control kidneys. Proliferative LN glomeruli are marked by podocyte loss with immune infiltration dominated by CD45RO+, HLA-DR+ memory CD4 and CD8 T-cells, and CD163+ macrophages, with similar changes in tubulointerstitial regions. Macrophages are the predominant HLA-DR expressing antigen presenting cells with little expression elsewhere, while macrophages and T-cells predominate cellular crescents. End-stage sclerotic glomeruli are encircled by an acellular fibro-epithelial Bowman's space surrounded by immune infiltrates, all enmeshed in fibronectin. Proliferative LN also shows signs indicative of epithelial to mesenchymal plasticity of tubular cells and parietal epithelial cells. IMC enabled proteomics is a powerful tool to delineate the spatial architecture of LN at the protein level.

Original languageEnglish
Article number109713
JournalClinical Immunology
Volume254
DOIs
StatePublished - Sep 2023
Externally publishedYes

Keywords

  • IMC
  • Imaging mass cytometry
  • Imaging mass cytometry proteomics
  • Kidney imaging mass cytometry
  • Lupus nephritis
  • Multiplexed imaging of human kidney
  • Proliferative LN

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