ORIGINAL RESEARCH article
Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1578359
This article is part of the Research TopicHunting for Inflammation Mediators: Identifying Novel Biomarkers for Autoimmune and Autoinflammatory DiseasesView all 9 articles
Serum Cystatin C as a Potential Biomarker for Generalized Acetylcholine Receptor Antibody-Positive Myasthenia Gravis
Provisionally accepted
He Dingxian1
Huahua Zhong1
Jin Lei1Ran Chen1
Zongtai Wu2
Rui Zhao1
Xiao Huan1Chong Yan1
Jie Song1
Jianying Xi1
Chongbo Zhao1
Shanfeng Zhu3
Sushan Luo1*- 1Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China
- 2University of Cambridge, Cambridge, England, United Kingdom
- 3Fudan University, Shanghai, Shanghai Municipality, China
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Objective: To identify new metabolic biomarkers associated with myasthenia gravis (MG).Methods: We analyzed 285 potential metabolic molecules from UK Biobank (UKB) for MG patients and identified elevated serum cystatin C (Cys-C). Validation was performed using laboratory data, ELISA, and clinical information from Chinese (CHN) acetylcholine receptor antibody (AChR-Ab) positive generalized MG (gMG) cohorts. We assessed cytokines/chemokines/complements and peripheral blood T lymphocytes using Luminex assays and flow cytometry. MG-relevant scores including myasthenia gravis activities of daily living score (MG-ADL) and quantitative myasthenia gravis score (QMG) were prospectively collected and retrospectively analyzed. The correlations between serum Cys-C and the ratio of T helper 1 (Th1)/Th2 were assessed.Results: Serum Cys-C levels were significantly elevated in MG patients compared to healthy controls in both UKB cohorts and Chinese MG cohorts (CHN) (UKB: 0.99 ± 0.20 vs. 0.86 ± 0.12 mg/L, p = 2.26E-41; CHN: 1.08 ± 0.30 vs. 0.87 ± 0.13 mg/L, p = 4.83E-08). Higher serum Cys-C levels were found in MG patients with high disease burden, as stratified by MG-ADL score. Serum Cys-C correlated with MG scores, including QMG (R = 0.40, p = 3.90E-03) and MG-ADL scores (R = 0.42, p = 2.40E-03). The ratio of Th1/Th2 correlated well with the serum Cys-C (R = 0.29, p = 3.10E-02).Conclusions: Serum Cys-C levels were significantly elevated in AChR-Ab positive gMG patients and correlated with disease severity and Th1/Th2 ratio, suggesting its potential as an efficient biomarker for predicting the clinical severity of MG. Future prospective cohort studies with a large sample size are expected to validate these findings.
Keywords: Myasthenia Gravis, Cystatin C, biomarker, T helper cell, Clinical severity
Received: 17 Feb 2025; Accepted: 14 Apr 2025.
Copyright: © 2025 Dingxian, Zhong, Lei, Chen, Wu, Zhao, Huan, Yan, Song, Xi, Zhao, Zhu and Luo. 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: Sushan Luo, Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China
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