TY - JOUR
T1 - Molecular architecture of proliferative lupus nephritis as elucidated using 50-plex imaging mass cytometry proteomics
AU - Louis Sam Titus, Anto Sam Crosslee
AU - Tan, Ying
AU - Tran, Phuongthy
AU - Lindblom, Julius
AU - Ivbievbiokun, Maryann
AU - Xu, Yitian
AU - Zheng, Junjun
AU - Parodis, Ioannis
AU - Cai, Qi
AU - Chang, Anthony
AU - Chen, Shu-Hsia
AU - Zhao, Minghui
AU - Mohan, Chandra
N1 - Funding Information:
This work is supported in part by NIH grant RO1 AR074096 and the Lupus Research Alliance.
Publisher Copyright:
© 2023
PY - 2023/9
Y1 - 2023/9
N2 - 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.
AB - 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.
KW - Humans
KW - Lupus Nephritis
KW - Proteomics
KW - Kidney Glomerulus/metabolism
KW - Kidney/metabolism
KW - Image Cytometry
KW - Kidney imaging mass cytometry
KW - Multiplexed imaging of human kidney
KW - Imaging mass cytometry proteomics
KW - Lupus nephritis
KW - Proliferative LN
KW - Imaging mass cytometry
KW - IMC
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U2 - 10.1016/j.clim.2023.109713
DO - 10.1016/j.clim.2023.109713
M3 - Article
C2 - 37516396
SN - 1521-6616
VL - 254
SP - 109713
JO - Clinical immunology (Orlando, Fla.)
JF - Clinical immunology (Orlando, Fla.)
M1 - 109713
ER -