Intravenous Immunoglobulin Elevates Regulatory T Cells in Guillain-Barré Syndrome: A Potential Biomarker of Therapeutic Response

IF 3.9 3区医学 Q1 CLINICAL NEUROLOGY

Journal of the Peripheral Nervous System Pub Date : 2025-06-25 DOI:10.1111/jns.70039

Israt Jahan, Rasel Ahmed, Jigishu Ahmed, Nure Alam Afsar, Pritha Promita Biswas, Sarah Khurshid, Quazi Deen Mohammad, Hubert P. Endtz, Ruth Huizinga, Bart C. Jacobs, Zhahirul Islam

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Abstract

Background and Aims

Intravenous immunoglobulin (IVIg) is the primary treatment for Guillain-Barré syndrome (GBS), yet its immunological mechanisms underlying variable clinical outcomes remain unclear. This study investigated the immunomodulatory effect of IVIg on regulatory T cells (Tregs), cytokines, and their association with treatment response and clinical outcomes.

Methods

In this prospective case-controlled study, 57 GBS patients and 57 age- and sex-matched healthy controls (HCs) were investigated. CD4⁺CD25⁺FoxP3⁺ Treg percentages, cytokine production (IL-10, TNF-α, IFN-γ, and IL-12), and serum C3 levels were measured using flow cytometry, Luminex assay, and turbidimetric methods, respectively. Treatment response was defined as ≥ 1-point GBS-disability score improvement during evaluation.

Results

GBS patients exhibited lower CD4⁺CD25⁺FoxP3⁺ Tregs frequencies compared to HCs (p = 0.006), which were inversely associated with serum C3 levels (p = 0.003) during the acute phase. At 4 weeks post-onset, patients with normal C3 levels (90–180 mg/dL) exhibited higher Treg frequencies (p = 0.005) compared to acute GBS, whereas patients with persistently elevated C3 levels showed reduced Treg percentage (p = 0.009). Among I VIg-treated patients, Tregs significantly increased at 2 and 4 weeks post-treatment, alongside significantly higher IL-10 and lower TNF-α, IFN-γ, and IL-12 levels at 4 weeks. However, patients with supportive care showed no such changes in Tregs and cytokine levels. Furthermore, Tregs elevated significantly in patients responsive to IVIg at 2 and 4 weeks (p < 0.05), but not in non-responsive or supportive care patients.

Interpretation

IVIg treatment modulates immune dysregulation in GBS by expanding CD4⁺CD25⁺FoxP3⁺ Tregs and altering cytokines and serum C3 levels, which are associated with clinical improvement. These findings indicate Tregs as potential biomarkers for monitoring initial clinical response to IVIg in GBS.

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静脉注射免疫球蛋白提高格林-巴勒综合征的调节性T细胞：治疗反应的潜在生物标志物

背景和目的静脉注射免疫球蛋白（IVIg）是格林-巴- 综合征（GBS）的主要治疗方法，但其免疫学机制尚不清楚。本研究探讨了IVIg对调节性T细胞（Tregs）、细胞因子的免疫调节作用，以及它们与治疗反应和临床结果的关系。方法在这项前瞻性病例对照研究中，对57名GBS患者和57名年龄和性别匹配的健康对照（hc）进行了调查。CD4+CD25+FoxP3+ Treg百分比、细胞因子生成（IL-10、TNF-α、IFN-γ和IL-12）和血清C3水平分别采用流式细胞术、Luminex法和比浊法测定。治疗反应定义为评估时gbs -残疾评分改善≥1分。结果GBS患者CD4+CD25+FoxP3+ Tregs频率低于hcc患者（p = 0.006），其与急性期血清C3水平呈负相关（p = 0.003）。发病后4周，与急性GBS相比，C3水平正常（90-180 mg/dL）的患者Treg频率更高（p = 0.005），而C3水平持续升高的患者Treg百分比降低（p = 0.009）。在I名接受vigg治疗的患者中，Tregs在治疗后2周和4周显著升高，同时IL-10水平显著升高，TNF-α、IFN-γ和IL-12水平显著降低。然而，接受支持性治疗的患者在Tregs和细胞因子水平上没有这种变化。此外，在第2周和第4周对IVIg有反应的患者中，Tregs显著升高（p < 0.05），而在无反应或支持治疗的患者中则没有升高。IVIg治疗通过增加CD4+CD25+FoxP3+ Tregs和改变细胞因子和血清C3水平来调节GBS的免疫失调，这与临床改善有关。这些发现表明treg是监测GBS患者对IVIg初始临床反应的潜在生物标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of the Peripheral Nervous System 医学-临床神经学

CiteScore

6.10

自引率

7.90%

发文量

审稿时长

>12 weeks

期刊介绍： The Journal of the Peripheral Nervous System is the official journal of the Peripheral Nerve Society. Founded in 1996, it is the scientific journal of choice for clinicians, clinical scientists and basic neuroscientists interested in all aspects of biology and clinical research of peripheral nervous system disorders. The Journal of the Peripheral Nervous System is a peer-reviewed journal that publishes high quality articles on cell and molecular biology, genomics, neuropathic pain, clinical research, trials, and unique case reports on inherited and acquired peripheral neuropathies. Original articles are organized according to the topic in one of four specific areas: Mechanisms of Disease, Genetics, Clinical Research, and Clinical Trials. The journal also publishes regular review papers on hot topics and Special Issues on basic, clinical, or assembled research in the field of peripheral nervous system disorders. Authors interested in contributing a review-type article or a Special Issue should contact the Editorial Office to discuss the scope of the proposed article with the Editor-in-Chief.