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Abstract: SA-PO823

Molecular Classification of Lupus Nephritis Based on Immune Pathway Profiling: Correlations with Histological Class and Clinical Manifestations

Session Information

Category: Glomerular Diseases

  • 1401 Glomerular Diseases: From Inflammation to Fibrosis

Author

  • Zhang, Danting, The University of Hong Kong Li Ka Shing Faculty of Medicine, Hong Kong, Hong Kong

Group or Team Name

  • Dr. Yap, Yat Hin Desmond Team.
Background

LN (lupus nephritis) ISN/RPS histopathological classification is the gold standard for assessment, however, does not inform the underlying immunological aberrations. A classification based on molecular typing of immune-related pathways may better stratify LN patients.

Methods

The expression matrix and clinical data were extracted from GEO and Nephroseq databases. ssGSEA method was used to derive immune phenotype with gene expression data. Hierarchical clustering with ssGSEA scores of selected gene sets classified LN tissues. Functional characterization and PPI of the DEGs were analyzed with Metascape. Kruskal-Walli test and chi-square test were performed to compare the clinical parameters.

Results

We calculated ssGESA scores of 96 immune-related gene sets in the glomerular and tubulointerstitial regions of LN kidney biopsy samples. Samples were then categorized into three clusters (Immune-Mild, Immune-Moderate, and Immune-Severe). Interferon-stimulated genes are a hallmark of LN. When compared to other groups, the Immune-Mild cluster from the glomerular region showed no T-cell activation pathway. The Immune-Mild (tubulointerstitial) showed minimal lymphocyte activation. PPI networks with MOCDE components further suggested that STAT1 and ISG15 are the core DEGs in different subgroups. The immune-Mild (Glomerular) showed a high prevalence of Class II and V LN, and Immune-Mild (Tubulointerstitial) showed more Class V LN. Immune-Severe group showed a higher degree of proteinuria and blood pressure but lower eGFR compared to the Immune Mild/Moderate groups.

Conclusion

A new molecular classification of LN based on the degree of immune pathway activation shows correlation with clinical manifestations, and may potentially guide personalized therapy in LN patients.

Figure 1. Features of Glomerular clusters.

Figure 2. Features of Tubulointerstitium clusters.