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ORIGINAL RESEARCH article

Front. Neurosci.
Sec. Neurodegeneration
Volume 18 - 2024 | doi: 10.3389/fnins.2024.1398653

Genetically predicted N-Acetyl-L-Alanine mediates the association between CD3 on activated & secreting Tregs and Guillain-Barre syndrome

Provisionally accepted
Qi Lyu Qi Lyu 1Lianlian Zhang Lianlian Zhang 2Yasuo Ding Yasuo Ding 1Zehao Liu Zehao Liu 1*
  • 1 Jiangsu Taizhou People's Hospital, Taizhou, China
  • 2 Yancheng First People's Hospital, Yancheng, Jiangsu, China

The final, formatted version of the article will be published soon.

    Objective: This study sought to explore the potential causal relationships among immune cell traits, Guillain-Barre syndrome (GBS) and metabolites. Methods: Employing a two-sample Mendelian randomization (MR) approach, the study investigated the causal associations between 731 immune cell traits, 1400 metabolite levels and GBS leveraging summary-level data from a genome-wide association study (GWAS). To ensure the reliability of our findings, we further assessed horizontal pleiotropy and heterogeneity and evaluated the stability of MR results using the Leave-one-out method. Results: This study revealed a causal relationship between CD3 on activated & secreting Tregs and GBS. Higher CD3 on activated & secreting Regulatory Tregs increased the risk of GBS (primary MR analysis odds ratio (OR)1.31/SD increase, 95% confidence interval (CI) 1.08-1.58, p = 0.005). There was no reverse causality for GBS on CD3 on activated & secreting Tregs (p = 0.36). Plasma metabolite N-Acetyl-L-Alanine (ALA) was significantly positively correlated with GBS by using the IVW method (OR=2.04, 95% CI, 1.26-3.30; p =0.00038). CD3 on activated & secreting Tregs was found to be positively associated with ALA risk (IVW method, OR, 1.04; [95% CI, 1.01-1.07], p =0.0078). Mediation MR analysis indicated the mediated proportion of CD3 on activated & secreting Tregs mediated by ALA was 10% (95%CI 2.63%, 17.4%).In conclusion, our study identified a causal relationship between the level of CD3 on activated & secreting Tregs and GBS by genetic means, with a considerable proportion of the effect mediated by ALA. In clinical practice, thus providing guidance for future clinical research.

    Keywords: Guillain-Barre Syndrome, Mendelian Randomization Analysis, Immune Cells traits, N-acetyl-L-alanine, Plasma metabolites

    Received: 05 Jun 2024; Accepted: 30 Aug 2024.

    Copyright: © 2024 Lyu, Zhang, Ding and Liu. 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: Zehao Liu, Jiangsu Taizhou People's Hospital, Taizhou, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.