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Urine Proteomics and Renal Single-Cell Transcriptomics Implicate Interleukin-16 in Lupus Nephritis
Andrea Fava1, Deepak A Rao2, Chandra Mohan3
1Johns Hopkins University, Baltimore, Maryland.
Arthritis & Rheumatology (Hoboken, N.J.)
|November 16, 2021
Summary
Urinary proteomics identified novel biomarkers for lupus nephritis (LN), including Interleukin-16 (IL-16), offering new ways to monitor kidney inflammation and treatment response noninvasively.
Area of Science:
- Nephrology
- Proteomics
- Immunology
Background:
- Current lupus nephritis (LN) treatments are effective in only 30% of patients.
- There is a critical need for novel therapeutic strategies and biomarkers for LN management.
Purpose of the Study:
- To develop mechanistic hypotheses and explore novel biomarkers in LN by analyzing longitudinal urinary proteomic profiles.
- To identify noninvasive urinary biomarkers for monitoring intrarenal biologic pathways and treatment response in LN patients.
Main Methods:
- Quantified 1,000 urinary proteins in 30 LN patients at diagnosis and at 3, 6, and 12 months post-treatment.
- Analyzed urinary proteome data with baseline clinical features and longitudinal trajectories.
- Evaluated intrarenal expression of candidate biomarkers using single-cell transcriptomics of renal biopsy sections.
Main Results:
- Identified 237 urinary biomarkers associated with LN, revealing pathways like chemotaxis and neutrophil activation.
- Interleukin-16 (IL-16), CD163, and transforming growth factor β correlated with intrarenal nephritis activity.
- Urinary IL-16 levels decreased with treatment response, and IL16 was highly expressed by infiltrating immune cells in LN kidneys.
Conclusions:
- Urine proteomics can noninvasively monitor active intrarenal biologic pathways in LN, potentially transforming diagnosis and management.
- IL-16 is implicated in LN pathogenesis, serving as a potential therapeutic target and biomarker.
