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Abstract: SA-PO928

Identification of New Therapeutic Targets of Arsenic Trioxide for Lupus Nephritis: Machine Learning Bioinformatics and In Vitro Studies

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Xie, Ruiyan, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
  • Zhang, Danting, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
  • Sher, Ka Ho Jason, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
  • Yap, Yat Hin Desmond, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
Background

Lupus nephritis (LN) is a serious complication of systemic lupus nephritis (SLE). Preliminary study suggested that low-dose ATO treatment in active SLE patients was associated with reduced flare rates, but the underlying mechanisms have not well characterized.

Methods

The potential targets of differentially expressed genes (DEGs) from human SLE and LN PBMCs datasets were identified by bioinformatic analysis and network pharmacology. Characteristic hub genes were further selected using machine learning method. The relationship between the potential targets and immune cells was also examined.

Results

Twelve predicting immune related intersection DEGs in SLE were identified.
KEGG pathway analysis indicated that ATO could attenuate IL-17 signaling pathway (p=1.67E-18), and TNF signaling pathway (p=5.77E-11) in SLE. Five genes of features importance were selected by three machine learning models, in which MMP9 showed the highest performance in predicting SLE development (ROC AUC: 0.942). MMP9 also showed positive correlations with macrophages and neutrophils in ssGSEA analysis (r=0.88 and 0.66 respectively). Our in vitro studies further demonstrated that ATO treatment downregulated MMP9 expression in PBMCs obtained from LN patients during disease remission (n=5).

Conclusion

ATO can attenuate LN via reduction of MMP9 expression in PBMCs and different inflammatory pathways.

Figure 1. Intersection immune associated genes of arsenic trioxide in systemic lupus erythematosus (SLE).

Figure 2. MMP9 was selected as the hub target in systemic lupus erythematosus (SLE).