Potential Small Molecules for Therapy of Lupus Nephritis Based on Genetic Effect and Immune Infiltration

Biomed Res Int. 2022 Apr 23:2022:2259164. doi: 10.1155/2022/2259164. eCollection 2022.

Abstract

Lupus nephritis (LN) is the most common and significant complication of systemic lupus erythematosus (SLE) due to its poor prognosis and mortality rates in SLE patients. There is a critical need for new drugs as the pathogenesis of LN remains to be elucidated and immunosuppressive therapy comes with many deficiencies. In this study, 23 hub genes (IFI6, PLSCR1, XAF1, IFI16, IFI44, MX1, IFI44L, IFIT3, IFIT2, IFI27, DDX58, EIF2AK2, IFITM1, RTP4, IFITM3, TRIM22, PARP12, IFIH1, OAS1, HERC6, RSAD2, DDX60, and MX2) were identified through bioinformatics and network analysis and are closely related to interferon production and function. Interestingly, immune cell infiltration analysis and correlation analysis demonstrate a positive correlation between the expression of 23 hub genes and monocyte infiltration in glomeruli and M2 macrophage infiltration in the tubulointerstitium of LN patients. Additionally, the CTD database, DsigDB database, and DREIMT database were used to explore the bridging role of genes in chemicals and LN as well as the potential influence of these chemicals on immune cells. After comparison and discussion, six small molecules (Acetohexamide, Suloctidil, Terfenadine, Prochlorperazine, Mefloquine, and Triprolidine) were selected for their potential ability in treating lupus nephritis.

MeSH terms

  • Computational Biology
  • Female
  • Gene Expression
  • Genes, Regulator
  • Humans
  • Lupus Erythematosus, Systemic* / genetics
  • Lupus Nephritis* / drug therapy
  • Lupus Nephritis* / genetics
  • Male
  • Membrane Proteins / genetics
  • RNA-Binding Proteins / genetics

Substances

  • IFITM3 protein, human
  • Membrane Proteins
  • RNA-Binding Proteins