Effect of tacrolimus on soluble costimulatory molecules in patients with refractory myasthenia gravis

Hui Wu; Lan Chen; Xiaoling Zhou; Yanshi Wu; Yu Yan; Yibei Zhu; Chongbo Zhao; Qun Xue

doi:10.1016/j.jneuroim.2022.577955

Effect of tacrolimus on soluble costimulatory molecules in patients with refractory myasthenia gravis

J Neuroimmunol. 2022 Nov 15:372:577955. doi: 10.1016/j.jneuroim.2022.577955. Epub 2022 Aug 27.

Authors

Hui Wu¹, Lan Chen², Xiaoling Zhou³, Yanshi Wu⁴, Yu Yan⁴, Yibei Zhu⁴, Chongbo Zhao⁵, Qun Xue⁶

Affiliations

¹ Department of Neurology, Jing'an District Centre Hospital of Shanghai, Shanghai, China.
² Department of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China; Department of Neurology, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
³ Department of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
⁴ Department of Immunology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou, Jiangsu, China.
⁵ Huashan Rare Disease Center, Department of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China. Electronic address: zhao_chongbo@fudan.edu.cn.
⁶ Department of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China. Electronic address: qxue_sz@163.com.

PMID: 36054935
DOI: 10.1016/j.jneuroim.2022.577955

Abstract

Objectives: To investigate the expression and possible role of soluble costimulatory molecules in the treatment of refractory myasthenia gravis.

Methods: Thirty-two patients with refractory myasthenia gravis were enrolled into this study and given tacrolimus 3 mg/day. At the beginning of treatment and 12 months follow-up period, clinical data were collected and recorded. The clinical classification of myasthenia gravis Foundation (MGFA) was performed. The MGFA-quantitative myasthenia gravis score (MGFA-QMGS), manual muscle test (MMT), MG activity of daily living (MG-ADL) and the activity of daily living (MG-ADL), the 15-item myasthenia gravis quality of life (MG QOL-15) and the dose change of prednisone were used to evaluate the efficacy. The expression levels of soluble costimulatory molecules and their ligands (sPD-1/sPD-L1, sICOS/sICOSL, sCD40/sCD40L), soluble CD25 and IL-2 in serum were determined by enzyme-linked immunosorbent assay (ELISA).

Results: We observed that oral administration of 3 mg tacrolimus daily for 1 year can significantly improve the clinical symptoms of patients with refractory myasthenia gravis, which is characterized by a significant reduction in clinical scores, such as QMG, MMT, ADL, MGQOL-15, and a reduction daily oral prednisolone (PSL) dose (P < 0.0001).We also found that the levels of plasma sPD-1, sCD40, IL-2 in refractory MG patients increased significantly, and those decreased significantly 12 months after tacrolimus treatment (P < 0.05). The level of sCD25 was negatively correlated with clinical severity scores (P < 0.05). After tacrolimus treatment, the level of sPD-L1 increased although there was no significant difference.

Conclusion: Tacrolimus could relieve the symptoms of refractory MG and significantly decrease the levels of plasma sPD-1, sICOSL, sCD40, sCD25 and IL-2. Soluble costimulatory molecules might be potential biomarkers for MG and tacrolimus treatment.

Keywords: Myasthenia gravis; Prognosis; Refractory myasthenia gravis; Risk factors; Soluble costimulatory molecules; Tacrolimus.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Humans
Interleukin-2
Myasthenia Gravis* / drug therapy
Prednisolone / therapeutic use
Prednisone / therapeutic use
Quality of Life
Tacrolimus* / therapeutic use
Transcription Factors

Substances

Interleukin-2
Prednisolone
Prednisone
Tacrolimus
Transcription Factors