IGFBP2 function as a novel biomarker for active lupus nephritis.

Area of Science:

• Nephrology
• Immunology
• Biochemistry

Background:

• Lupus nephritis (LN) requires novel diagnostic and therapeutic targets.
• Insulin-like growth factor-binding protein 2 (IGFBP2) is understudied in LN pathogenesis.

Purpose of the Study:

• To identify novel biomarkers for active LN.
• To investigate the role of IGFBP2 in LN diagnosis and treatment.

Main Methods:

• Utilized TMT-liquid chromatography-triple quadrupole mass spectrometry (TMT-LC-MS/MS) and RNA-seq.
• Validated IGFBP2 levels in active LN patients.
• Assessed IGFBP2's diagnostic efficiency using ROC curves.
• Investigated IGFBP2 neutralization effects in MRL/lpr mouse models.

Main Results:

• Identified dysregulated proteins and mRNA in active LN patients.
• IGFBP2 levels significantly increased in active LN and correlated with SLE activity.
• Plasma IGFBP2 demonstrated high diagnostic efficiency for active LN (AUC = 0.992).
• Neutralizing IGFBP2 improved nephritis in mice, downregulated AKT/mTOR/4E-BP1 pathway, and modulated CD4+ T cell and Treg ratios.

Conclusions:

• IGFBP2 is a specific biomarker for active LN and a predictor of poor prognosis.
• Blocking IGFBP2 represents a potential therapeutic strategy for LN.
• IGFBP2 influences CD4+ T cell activation and Treg balance, impacting LN pathology.