ORIGINAL RESEARCH article
Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders
Urinary Extracellular Vesicle Metabolomic Profiling Reveals a Distinct Molecular Signature for the Non-Invasive Diagnosis of Lupus Nephritis
Provisionally accepted
- Department of Clinical Laboratory, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China
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Background: Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE), underscoring an urgent need for non-invasive diagnostic biomarkers. Objective: This study aimed to define the metabolomic signature of urinary extracellular vesicles (uEVs) in LN and to identify novel biomarkers for precision diagnosis. Methods: uEVs were isolated from urine samples of 29 SLE patients with LN, 22 SLE patients without renal involvement, and 20 healthy controls (HCs) using a standardized precipitation-based protocol. uEVs were rigorously characterized in accordance with the Minimal Information for Studies of Extracellular Vesicles (MISEV) guidelines, including transmission electron microscopy, nanoparticle tracking analysis, and the assessment of canonical EV markers. Comprehensive untargeted metabolomic profiling of uEVs was subsequently performed using liquid chromatography–tandem mass spectrometry (LC–MS/MS). Results: Among the 897 metabolites identified, 284 were significantly dysregulated in patients with LN. Machine learning–based feature prioritization using a random forest algorithm identified a panel of ten candidate metabolites. Notably, three metabolites—glucosylsphingosine, phosphatidylethanolamine N-methylated (PE-NMe), and PC(20:5/TXB2)—demonstrated excellent discriminatory performance for differentiating LN from non-renal SLE, with areas under the receiver operating characteristic curve (AUCs) of 0.912, 0.906, and 0.897, respectively. Conclusion: We identified a distinct uEV metabolic signature in LN and developed a robust, non-invasive biomarker panel. This strategy holds significant promise for the early detection and personalized management of LN, offering a compelling alternative to invasive renal biopsy.
Keywords: diagnostic biomarkers, Lupus Nephritis, Metabolomic profiling, ROC Curve, urinary extracellular vesicles
Received: 07 Nov 2025; Accepted: 19 Jan 2026.
Copyright: © 2026 Zhang, Dong, Xie, Liu, Khan, Rui, Li and Yang. 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: Ping Yang
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