ORIGINAL RESEARCH article
Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders
This article is part of the Research TopicAutoimmune Glomerular Diseases: From Molecular Mechanisms to Precision TherapiesView all 6 articles
Elevated serum soluble α3(IV)NC1 correlates with kidney injury and worse outcome in patients with anti-glomerular basement membrane disease
Provisionally accepted
- Peking University First Hospital, Bejing, China
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Background: Anti-glomerular basement membrane (GBM) disease is the most severe form of autoimmune kidney diseases characterized by pathogenic autoantibodies against GBM component, α3(IV)NC1. However, the status of circulating soluble α3(IV)NC1 (also known as tumstatin) in patients with anti-GBM disease and its clinical relevance remain unclear. The aim of this study was to investigate the serum soluble α3(IV)NC1 level [ss-α3(IV)NC1] in patients with anti-GBM disease, and to analyze its association to clinical characteristics. Methods: Seventy patients with anti-GBM disease and 30 healthy individuals were enrolled. Ss-α3(IV)NC1 was measured by enzyme-linked immunosorbent assay. The level was compared and analyzed with clinical-pathological features and kidney outcome, and the statistical significance was determined. Results: Ss-α3(IV)NC1 concentrations were elevated in 41 (58.6%) patients with anti-GBM disease and 0 (0.0%) healthy individuals. They were significantly higher in patients with anti-GBM disease (18.32 ± 9.56 ng/mL) than those in healthy individuals (5.84 ± 2.78 ng/mL) (P < 0.001). Ss-α3(IV)NC1 correlated with age (r = 0.385, P = 0.001), serum creatinine (r = 0.286, P = 0.016), eGFR (r = -0.304, P = 0.010), crescents (r = 0.339, P = 0.030), and normal glomeruli (r = -0.354, P = 0.023). Kaplan–Meier analysis revealed that patients with elevated ss-α3(IV)NC1 had a worse kidney outcome than those with normal level (P = 0.011). Conclusions: The ss-α3(IV)NC1 was abnormally elevated in patients with anti-GBM disease. Elevated ss-α3(IV)NC1 was associated with the disease severity in anti-GBM disease. The role of these elevated levels warrants further investigation.
Keywords: Anti-Glomerular Basement Membrane Disease, Clinical significance, Outcome, Soluble antigen, α3(IV)NC1
Received: 19 Oct 2025; Accepted: 03 Feb 2026.
Copyright: © 2026 Kuang, Wan, Cui, Zhao and Jia. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Huang Kuang
Xiao-yu Jia
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