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

doi:10.1016/j.clim.2023.109713

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 journal › Article › peer-review

9 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 language	English (US)
Article number	109713
Pages (from-to)	109713
Journal	Clinical immunology (Orlando, Fla.)
Volume	254
DOIs	https://doi.org/10.1016/j.clim.2023.109713
State	Published - Sep 2023

Keywords

Humans
Lupus Nephritis
Proteomics
Kidney Glomerulus/metabolism
Kidney/metabolism
Image Cytometry
Kidney imaging mass cytometry
Multiplexed imaging of human kidney
Imaging mass cytometry proteomics
Lupus nephritis
Proliferative LN
Imaging mass cytometry
IMC

ASJC Scopus subject areas

Immunology and Allergy
Immunology

Divisions

Medical Oncology

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10.1016/j.clim.2023.109713

Cite this

Louis Sam Titus, A. S. C., Tan, Y., Tran, P., Lindblom, J., Ivbievbiokun, M., Xu, Y., Zheng, J., Parodis, I., Cai, Q., Chang, A., Chen, S.-H., Zhao, M., & Mohan, C. (2023). Molecular architecture of proliferative lupus nephritis as elucidated using 50-plex imaging mass cytometry proteomics. Clinical immunology (Orlando, Fla.), 254, 109713. Article 109713. https://doi.org/10.1016/j.clim.2023.109713

Louis Sam Titus, ASC, Tan, Y, Tran, P, Lindblom, J, Ivbievbiokun, M, Xu, Y, Zheng, J, Parodis, I, Cai, Q, Chang, A, Chen, S-H, Zhao, M & Mohan, C 2023, 'Molecular architecture of proliferative lupus nephritis as elucidated using 50-plex imaging mass cytometry proteomics', Clinical immunology (Orlando, Fla.), vol. 254, 109713, pp. 109713. https://doi.org/10.1016/j.clim.2023.109713

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

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.",

keywords = "Humans, Lupus Nephritis, Proteomics, Kidney Glomerulus/metabolism, Kidney/metabolism, Image Cytometry, Kidney imaging mass cytometry, Multiplexed imaging of human kidney, Imaging mass cytometry proteomics, Lupus nephritis, Proliferative LN, Imaging mass cytometry, IMC",

author = "\{Louis Sam Titus\}, \{Anto Sam Crosslee\} and Ying Tan and Phuongthy Tran and Julius Lindblom and Maryann Ivbievbiokun and Yitian Xu and Junjun Zheng and Ioannis Parodis and Qi Cai and Anthony Chang and Shu-Hsia Chen and Minghui Zhao and Chandra Mohan",

note = "Funding Information: This work is supported in part by NIH grant RO1 AR074096 and the Lupus Research Alliance. Publisher Copyright: {\textcopyright} 2023",

year = "2023",

month = sep,

doi = "10.1016/j.clim.2023.109713",

language = "English (US)",

volume = "254",

pages = "109713",

journal = "Clinical immunology (Orlando, Fla.)",

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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

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.

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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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SN - 1521-6616

VL - 254

SP - 109713

JO - Clinical immunology (Orlando, Fla.)

JF - Clinical immunology (Orlando, Fla.)

M1 - 109713

ER -

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

Abstract

Keywords

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