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Peer-reviewedCC BY 4.0Frontiers in Neurology

Association of serum Sema4D and ANGPTL4 levels with disease severity and prognosis in myasthenia gravis patients

  • Wenqian Li1
  • Mengsi Zhang1
  • Zhibo Wang1
  • Chundong Gong1
  • Lu Sun1
  • Wenjing Feng1
  • Guoyan Qi2
  • Ying Yang2
  • Fuda Yu1
  1. 1Department of Neuroelectrophysiology, Shijiazhuang People’s Hospital
  2. 2Center for Myasthenia Gravis, Shijiazhuang People’s Hospital
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Abstract

Objective: To investigate the relationship of serum semaphorin 4D (Sema4D) and angiopoietin-like protein 4 (ANGPTL4) levels with disease severity and prognosis in anti–acetylcholine receptor (AChR) antibody–positive myasthenia gravis (MG) patients.

Methods: Between December 2023 and April 2025, 468 anti-AChR antibody–positive MG patients hospitalized at our center were prospectively enrolled and divided into good- and poor-prognosis groups according to whether they achieved minimal manifestations (MM) or better status at the 1-year follow-up. Healthy controls were also enrolled. Serum Sema4D and ANGPTL4 levels were measured by enzyme-linked immunosorbent assay (ELISA). Correlations were evaluated by Spearman’s rank correlation. Multivariable logistic regression was used to identify independent risk factors for poor prognosis. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive value of the two biomarkers alone and in combination, and clinical and combined models were developed to evaluate the biomarkers’ incremental predictive value.

Results: Serum Sema4D and ANGPTL4 levels were significantly higher in MG patients than in healthy controls (both p < 0.001). Compared with the good-prognosis group, the poor-prognosis group had higher proportions of Myasthenia Gravis Foundation of America (MGFA) class IV-V, dysphagia, and thymoma, and higher Myasthenia Gravis Quality of Life 15-item revised (MG-QoL15r) and Controlling Nutritional Status (CONUT) scores (all p < 0.05), and significantly higher levels of both biomarkers (both p < 0.05). Both Sema4D and ANGPTL4 correlated positively with MG-QoL15r and CONUT scores and with each other ( r = 0.431, p < 0.001). Multivariable logistic regression showed that MGFA class IV-V, dysphagia, thymoma, higher MG-QoL15r and CONUT scores, and elevated serum Sema4D and ANGPTL4 levels were all independent risk factors for poor prognosis (all p < 0.05). The combination of the two biomarkers yielded an area under the ROC curve (AUC) of 0.841, superior to either marker alone. Adding the biomarkers to the clinical model significantly improved prognostic discrimination, with the AUC increasing from 0.874 to 0.907 ( p = 0.0002).

Conclusion: Combined measurement of serum Sema4D and ANGPTL4 is associated with disease severity and poor prognosis in anti-AChR antibody–positive MG and shows good predictive value for patient prognosis.

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Cite

BibTeXRIS
BibTeX
@article{li2026association,
  title = {{Association of serum Sema4D and ANGPTL4 levels with disease severity and prognosis in myasthenia gravis patients}},
  author = {Wenqian Li and Mengsi Zhang and Zhibo Wang and Chundong Gong and Lu Sun and Wenjing Feng and Guoyan Qi and Ying Yang and Fuda Yu},
  journal = {Frontiers in Neurology},
  year = {2026},
  month = oct,
  doi = {10.3389/fneur.2026.1965303},
  url = {https://www.frontiersin.org/articles/10.3389/fneur.2026.1965303/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Association of serum Sema4D and ANGPTL4 levels with disease severity and prognosis in myasthenia gravis patients
AU  - Wenqian Li
AU  - Mengsi Zhang
AU  - Zhibo Wang
AU  - Chundong Gong
AU  - Lu Sun
AU  - Wenjing Feng
AU  - Guoyan Qi
AU  - Ying Yang
AU  - Fuda Yu
PY  - 2026
DA  - 2026/10/26
JO  - Frontiers in Neurology
DO  - 10.3389/fneur.2026.1965303
UR  - https://www.frontiersin.org/articles/10.3389/fneur.2026.1965303/full
AB  - Objective: To investigate the relationship of serum semaphorin 4D (Sema4D) and angiopoietin-like protein 4 (ANGPTL4) levels with disease severity and prognosis in anti–acetylcholine receptor (AChR) antibody–positive myasthenia gravis (MG) patients.  Methods: Between December 2023 and April 2025, 468 anti-AChR antibody–positive MG patients hospitalized at our center were prospectively enrolled and divided into good- and poor-prognosis groups according to whether they achieved minimal manifestations (MM) or better status at the 1-year follow-up. Healthy controls were also enrolled. Serum Sema4D and ANGPTL4 levels were measured by enzyme-linked immunosorbent assay (ELISA). Correlations were evaluated by Spearman’s rank correlation. Multivariable logistic regression was used to identify independent risk factors for poor prognosis. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive value of the two biomarkers alone and in combination, and clinical and combined models were developed to evaluate the biomarkers’ incremental predictive value.  Results: Serum Sema4D and ANGPTL4 levels were significantly higher in MG patients than in healthy controls (both p < 0.001). Compared with the good-prognosis group, the poor-prognosis group had higher proportions of Myasthenia Gravis Foundation of America (MGFA) class IV-V, dysphagia, and thymoma, and higher Myasthenia Gravis Quality of Life 15-item revised (MG-QoL15r) and Controlling Nutritional Status (CONUT) scores (all p < 0.05), and significantly higher levels of both biomarkers (both p < 0.05). Both Sema4D and ANGPTL4 correlated positively with MG-QoL15r and CONUT scores and with each other ( r = 0.431, p < 0.001). Multivariable logistic regression showed that MGFA class IV-V, dysphagia, thymoma, higher MG-QoL15r and CONUT scores, and elevated serum Sema4D and ANGPTL4 levels were all independent risk factors for poor prognosis (all p < 0.05). The combination of the two biomarkers yielded an area under the ROC curve (AUC) of 0.841, superior to either marker alone. Adding the biomarkers to the clinical model significantly improved prognostic discrimination, with the AUC increasing from 0.874 to 0.907 ( p = 0.0002).  Conclusion: Combined measurement of serum Sema4D and ANGPTL4 is associated with disease severity and poor prognosis in anti-AChR antibody–positive MG and shows good predictive value for patient prognosis.
SN  - 1664-2295
ER  -