In silico analysis highlights elevation of epithelial-to-mesenchymal transition characteristics in non-responding lupus nephritis patients

Abstract

Objective

Lupus nephritis (LN) is a common complication in a significant proportion of systemic lupus erythematosus (SLE) patients. As a chronic autoimmune disease, LN leads to renal failure, substantially impacting patient quality of life and mortality rates. Current LN treatments primarily involve traditional immunosuppressants, such as azathioprine and mycophenolate mofetil (MMF). However, a subset of patients exhibits poor responsiveness to these therapies.

Methods

To identify genes specifically upregulated in this non-responder group, we analyzed RNA-sequencing data from the tubulointerstitial regions of LN patients and single-cell RNA-sequencing data from non-response LN patients, using datasets obtained from public databases.

Results

This analysis revealed an increased epithelial-to-mesenchymal transition (EMT) signature in the LN patients, and identified COL3A1, TNC, and PDGFRA as commonly upregulated genes in both general LN patients and non-responder LN patients. Further validation using single-cell RNA-sequencing confirmed that these genes are predominantly expressed in renal tubular epithelial cells. Furthermore, analysis of three additional independent LN datasets confirmed that COL3A1, TNC, and PDGFRA were significantly upregulated in the tubulointerstitial regions of other LN patient cohorts.

Conclusion

This study suggests that the non-responder group may exhibit enhanced EMT features, particularly involving the upregulation of COL3A1, TNC, and PDGFRA in the tubulointerstitial region. Therefore, these findings may aid in identifying potential biomarkers for difficult-to-treat patients and offer valuable insights into possible therapeutic targets for LN management.