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Urinary V-Set Ig Domain-Containing Protein 4 and Immune Complexes for Tracking Lupus Nephritis and Renal Pathology
Aygun Teymur1, Chenling Tang1, Fariz Nazir1
1University of Houston, Houston, Texas.
ACR Open Rheumatology
|May 7, 2025
Summary
Urinary V-set Ig domain-containing protein 4 immune complexes (VSIG4-ICx) show promise as a novel noninvasive biomarker for lupus nephritis (LN). Elevated VSIG4-ICx levels correlate with disease activity, aiding in diagnosis and monitoring of LN.
Area of Science:
- Nephrology
- Immunology
- Biomarker Discovery
Background:
- Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus.
- Current diagnostic and monitoring methods for LN can be invasive and lack specificity.
Purpose of the Study:
- To investigate the formation of V-set Ig domain-containing protein 4 (VSIG4; also known as complement receptor of the Ig superfamily [CRIg]) immune complexes (ICxs) with IgG and C3 in LN kidneys.
- To evaluate urinary VSIG4 and VSIG4-ICx as potential noninvasive biomarkers for LN diagnosis and monitoring.
Main Methods:
- Immunofluorescence staining to detect VSIG4, IgG, and C3 deposition in kidney biopsies.
- Enzyme-linked immunosorbent assay (ELISA) to quantify urinary VSIG4 and VSIG4-ICx in patients with LN, healthy controls (HCs), and chronic kidney disease (CKD) patients.
Main Results:
- VSIG4, IgG, and C3 colocalized in the kidneys of LN patients, with increased VSIG4 expression in glomeruli.
- Significantly elevated urinary VSIG4 (free form and ICx) levels were observed in LN patients compared to HCs and CKD patients.
- Urinary VSIG4-ICx strongly correlated with clinical disease activity indices (SLEDAI, renal SLEDAI), renal function (eGFR), and complement levels (C3, C4).
Conclusions:
- VSIG4-ICx is a promising novel urine biomarker for lupus nephritis.
- Urinary VSIG4-ICx has potential clinical utility for the diagnosis and disease monitoring of LN.
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