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Immune Imbalance in Primary Membranous Nephropathy at Single-cell Resolution
Xuan Tie1,2,3, Zhiang Chen4, Shulei Yao1,2,3
1Department of Nephrology, Second Hospital of Shanxi Medical University, 030000 Taiyuan, Shanxi, China.
Frontiers in Bioscience (Landmark Edition)
|February 28, 2025
Summary
Primary membranous nephropathy (pMN) involves increased proinflammatory factors and antiviral responses, indicating potential disease progression. This study identifies biomarkers for stratifying high-risk pMN patients and suggests new therapeutic targets.
Area of Science:
- Nephrology
- Immunology
- Genomics
Background:
- Primary membranous nephropathy (pMN) can lead to end-stage renal disease (ESRD) without immunosuppressive therapy.
- The immunological drivers of pMN progression are not fully understood.
Purpose of the Study:
- To investigate the immunological mechanisms underlying pMN progression.
- To identify potential biomarkers for stratifying pMN patients and predicting prognosis.
Main Methods:
- Single-cell transcriptomic profiling of peripheral blood mononuclear cells (PBMCs) from pMN patients and healthy donors.
- Correlation analysis to identify disease biomarkers.
- Validation in an external cohort.
Main Results:
- Elevated expression of proinflammatory factors (e.g., IL1B, IFNG) and pattern recognition receptors (e.g., NLRP3, cGAS) in pMN patients.
- Upregulation of HLA-DQA1 and HLA-DRB1 in memory B cells.
- Increased expression of antiviral defense genes and negative correlation of genes like BST2 and SLC35F1 with eGFR in high-risk patients.
- Development of scoring systems for risk stratification.
Conclusions:
- Unveiled immunological insights into pMN pathogenesis.
- Identified numerous biomarkers and signaling pathways as potential therapeutic targets for high-risk pMN.
- Provided tools for distinguishing high-risk pMN patients.
