Precision medicine in systemic lupus erythematosus

Area of Science:

• Immunology
• Genetics
• Precision Medicine

Background:

• Systemic lupus erythematosus (SLE) is a complex autoimmune disease with highly variable clinical presentations and treatment responses.
• The underlying pathomechanisms of SLE are heterogeneous, contributing to significant differences among patients.
• Identifying genetic and epigenetic factors is crucial for understanding SLE's diverse manifestations.

Purpose of the Study:

• To explore the cellular and molecular heterogeneity of SLE.
• To facilitate the development of stratified treatment recommendations and precision medicine approaches for SLE.
• To highlight the role of genetic and epigenetic variations in SLE's clinical heterogeneity.

Main Methods:

• Analysis of phenotype-related loci (e.g., STAT4, IRF5, PDGF genes, HAS2, ITGAM, SLC5A11).
• Investigation of epigenetic variations including DNA methylation, histone modifications, and microRNAs.
• Application of immune profiling techniques such as flow cytometry, mass cytometry, transcriptomics, microarray analysis, and single-cell RNA sequencing.
• Identification of potential serum and urinary biomarkers.

Main Results:

• Specific genes (STAT4, IRF5, PDGF, HAS2, ITGAM, SLC5A11) are associated with SLE's clinical features and heterogeneity.
• Epigenetic variations significantly influence gene expression and cell function in SLE.
• Immune profiling techniques can predict individual therapy responses and patient outcomes.
• Novel biomarkers are essential for patient stratification based on long-term predictions and treatment response.

Conclusions:

• Dissecting SLE's heterogeneity is key to advancing precision medicine.
• Genetic and epigenetic factors play a significant role in SLE's diverse clinical phenotypes.
• Immune profiling and biomarker discovery are vital for personalized SLE management and predicting patient outcomes.