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Updated: Aug 28, 2026
Analyses of Proteinuria, Renal Infiltration of Leukocytes, and Renal Deposition of Proteins in Lupus-prone MRL/lpr Mice
Published on: June 8, 2022
T cell, M2 macrophage infiltration and collagen, fibronectin, VCAM-1 expression portend poor outcome in lupus
Sen Hee Tay1,2, Anto Sam Crosslee Louis Sam Titus3, Vinaika Maruvada3
1Division of Rheumatology and Allergy, National University Hospital, Singapore, Singapore.
Introduction:
Despite advances in lupus nephritis (LN) management, its heterogenous nature poses challenges in predicting treatment response. Multiplexed spatial proteomics offers a potential solution to dissect the heterogeneity of treatment response in LN.
Methods:
Renal response was assessed in 16 LN patients undergoing physician-directed induction therapy. Baseline biopsies from these patients were subjected to 34-plex spatial proteomics. A total of 53 glomerular and 49 tubulointerstitial regions of interest from these LN patients and renal cell carcinoma (RCC) controls were analyzed for spatial predictors of treatment response.
Results:
There were increased glomerular and tubulointerstitial immune infiltrates in LN kidneys compared to RCC controls, including CD45RO, HLA-DR, and CD68-positive cells. Interestingly, there was increased glomerular and interstitial collagen I, collagen IV deposition, and fibronectin extracellular matrix (ECM) proteins in class V compared to class IV LN. Glomerular and tubulointerstitial immune infiltrates and fibrosis in pre-treatment biopsies predicted non-response (NR) to immunosuppressive therapy, including leukocytes expressing CD45RO, HLA-DR, CD4, CD14, and CD163 and collagen I, collagen IV, and fibronectin expression. Increased tubular and parietal epithelial cell expression of the activation/injury marker VCAM-1 also marked treatment NR.
Discussion:
As defined by multiplexed spatial proteomics, increased infiltration of activated T cells and CD163+ M2 macrophages, glomerular and tubulointerstitial fibrosis, and heightened expression of the injury marker VCAM-1 portend poor response to immunosuppressive treatment in LN.
