Exploring New Therapeutic Targets for Myasthenia Gravis: A Plasma and Cerebrospinal Fluid Proteomics Mendelian Randomization Study

Yibo He; Hongmei  Miao; Yinying Chai; Qianran Hong; Yuxuan Song

doi:10.71321/ybarkw62

Authors

Yibo He The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine）
Hongmei Miao The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang Province, China
Yinying Chai The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang Province, China
Qianran Hong The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang Province, China
Yuxuan Song The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang Province, China

DOI:

https://doi.org/10.71321/ybarkw62

Keywords:

Myasthenia Gravis, Mendelian Randomization, Proteomics, Cerebrospinal Fluid Proteins, Colocalization, Therapeutic Target

Abstract

Background: Myasthenia Gravis (MG) is a chronic autoimmune neuromuscular disorder that severely impacts patients' quality of life. Identifying plasma and cerebrospinal fluid (CSF) proteins with a genetic causal relationship to MG may provide novel therapeutic targets.
Methods: This study employed the Mendelian randomization (MR) approach, in combination with Bayesian colocalization analysis, to assess the causal relationship between 4,185 plasma proteins and 832 CSF proteins and the risk of MG. Sensitivity analyses were also performed to validate the robustness of the MR results. Additionally, protein–protein interaction networks and candidate drug predictions were utilized to elucidate the complex interactions between proteins and identify potential drug targets.
Results: Three plasma proteins and five CSF proteins were significantly associated with MG risk. ALDH2, HSPA1A, PRSS8, MFRP, CTSH, SHBG, and TXNDC12 were found to increase MG risk, while IL36A was negatively correlated. Further colocalization analysis revealed strong evidence for the associations between PRSS8 and HSPA1A with MG (pph4 > 0.8), and substantial evidence for TXNDC12 and ALDH2 (0.8 > pph4 > 0.6).
Conclusion: This study employed proteomics-based MR to identify several plasma and CSF proteins significantly associated with the risk of MG. Notably, PRSS8, HSPA1A, TXNDC12, and ALDH2 emerge as potential therapeutic targets for MG. While these findings offer valuable insights into the pathological mechanisms of MG and the development of novel therapeutic strategies, further research is required to evaluate the feasibility and clinical efficacy of these candidate proteins.

Author Biographies

Hongmei Miao, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang Province, China

none
Yinying Chai, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang Province, China

none
Qianran Hong, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang Province, China

none
Yuxuan Song, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang Province, China

none

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