Serum cystatin C as a potential biomarker for generalized acetylcholine receptor antibody-positive myasthenia gravis

ObjectiveTo identify new metabolic biomarkers associated with myasthenia gravis (MG).MethodsWe 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 inform...

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Main Authors: Dingxian He, Huahua Zhong, Lei Jin, Ran Chen, Zongtai Wu, Rui Zhao, Xiao Huan, Chong Yan, Jie Song, Jianying Xi, Chongbo Zhao, Shanfeng Zhu, Sushan Luo
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-05-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1578359/full
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author Dingxian He
Huahua Zhong
Lei Jin
Ran Chen
Zongtai Wu
Rui Zhao
Xiao Huan
Chong Yan
Jie Song
Jianying Xi
Chongbo Zhao
Shanfeng Zhu
Shanfeng Zhu
Shanfeng Zhu
Sushan Luo
author_facet Dingxian He
Huahua Zhong
Lei Jin
Ran Chen
Zongtai Wu
Rui Zhao
Xiao Huan
Chong Yan
Jie Song
Jianying Xi
Chongbo Zhao
Shanfeng Zhu
Shanfeng Zhu
Shanfeng Zhu
Sushan Luo
author_sort Dingxian He
collection DOAJ
description ObjectiveTo identify new metabolic biomarkers associated with myasthenia gravis (MG).MethodsWe 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.ResultsSerum 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).ConclusionsSerum 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.
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spelling doaj-art-ebd6030921a24ecc8d4cf410ce5adde22025-08-20T02:16:18ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-05-011610.3389/fimmu.2025.15783591578359Serum cystatin C as a potential biomarker for generalized acetylcholine receptor antibody-positive myasthenia gravisDingxian He0Huahua Zhong1Lei Jin2Ran Chen3Zongtai Wu4Rui Zhao5Xiao Huan6Chong Yan7Jie Song8Jianying Xi9Chongbo Zhao10Shanfeng Zhu11Shanfeng Zhu12Shanfeng Zhu13Sushan Luo14Huashan Rare Disease Centre and Department of Neurology, Huashan Hospital, Shanghai Medical College, National Centre for Neurological Disorders, Fudan University, Shanghai, ChinaHuashan Rare Disease Centre and Department of Neurology, Huashan Hospital, Shanghai Medical College, National Centre for Neurological Disorders, Fudan University, Shanghai, ChinaHuashan Rare Disease Centre and Department of Neurology, Huashan Hospital, Shanghai Medical College, National Centre for Neurological Disorders, Fudan University, Shanghai, ChinaHuashan Rare Disease Centre and Department of Neurology, Huashan Hospital, Shanghai Medical College, National Centre for Neurological Disorders, Fudan University, Shanghai, ChinaDepartment of Public Health and Primary Care, University of Cambridge, Cambridge, United KingdomHuashan Rare Disease Centre and Department of Neurology, Huashan Hospital, Shanghai Medical College, National Centre for Neurological Disorders, Fudan University, Shanghai, ChinaHuashan Rare Disease Centre and Department of Neurology, Huashan Hospital, Shanghai Medical College, National Centre for Neurological Disorders, Fudan University, Shanghai, ChinaHuashan Rare Disease Centre and Department of Neurology, Huashan Hospital, Shanghai Medical College, National Centre for Neurological Disorders, Fudan University, Shanghai, ChinaHuashan Rare Disease Centre and Department of Neurology, Huashan Hospital, Shanghai Medical College, National Centre for Neurological Disorders, Fudan University, Shanghai, ChinaHuashan Rare Disease Centre and Department of Neurology, Huashan Hospital, Shanghai Medical College, National Centre for Neurological Disorders, Fudan University, Shanghai, ChinaHuashan Rare Disease Centre and Department of Neurology, Huashan Hospital, Shanghai Medical College, National Centre for Neurological Disorders, Fudan University, Shanghai, ChinaInstitute of Science and Technology for Brain-Inspired Intelligence and Ministry of Education (MOE) Frontiers Center for Brain Science, Fudan University, Shanghai, ChinaKey Laboratory of Computational Neuroscience and Brain-Inspired Intelligence (Fudan University), Ministry of Education, Shanghai, ChinaZhangjiang Fudan International Innovation Center, Fudan University, Shanghai, ChinaHuashan Rare Disease Centre and Department of Neurology, Huashan Hospital, Shanghai Medical College, National Centre for Neurological Disorders, Fudan University, Shanghai, ChinaObjectiveTo identify new metabolic biomarkers associated with myasthenia gravis (MG).MethodsWe 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.ResultsSerum 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).ConclusionsSerum 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.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1578359/fullmyasthenia graviscystatin CbiomarkerT helper cellclinical severity
spellingShingle Dingxian He
Huahua Zhong
Lei Jin
Ran Chen
Zongtai Wu
Rui Zhao
Xiao Huan
Chong Yan
Jie Song
Jianying Xi
Chongbo Zhao
Shanfeng Zhu
Shanfeng Zhu
Shanfeng Zhu
Sushan Luo
Serum cystatin C as a potential biomarker for generalized acetylcholine receptor antibody-positive myasthenia gravis
Frontiers in Immunology
myasthenia gravis
cystatin C
biomarker
T helper cell
clinical severity
title Serum cystatin C as a potential biomarker for generalized acetylcholine receptor antibody-positive myasthenia gravis
title_full Serum cystatin C as a potential biomarker for generalized acetylcholine receptor antibody-positive myasthenia gravis
title_fullStr Serum cystatin C as a potential biomarker for generalized acetylcholine receptor antibody-positive myasthenia gravis
title_full_unstemmed Serum cystatin C as a potential biomarker for generalized acetylcholine receptor antibody-positive myasthenia gravis
title_short Serum cystatin C as a potential biomarker for generalized acetylcholine receptor antibody-positive myasthenia gravis
title_sort serum cystatin c as a potential biomarker for generalized acetylcholine receptor antibody positive myasthenia gravis
topic myasthenia gravis
cystatin C
biomarker
T helper cell
clinical severity
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1578359/full
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