静脉注射免疫球蛋白可提高吉兰-巴雷综合征患者的调节性T细胞水平：一种潜在的治疗反应生物标志物。

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

作者信息

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

机构信息

Laboratory of Gut-Brain Axis, Infectious Diseases Division, icddr,b, Dhaka, Bangladesh.

Department of Medical Microbiology and Infectious Diseases, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.

出版信息

J Peripher Nerv Syst. 2025 Sep;30(3):e70039. doi: 10.1111/jns.70039.

DOI:10.1111/jns.70039

PMID:40558063

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. CD4CD25FoxP3 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 CD4CD25FoxP3 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 CD4CD25FoxP3 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.

摘要

背景与目的

静脉注射免疫球蛋白（IVIg）是吉兰-巴雷综合征（GBS）的主要治疗方法，但其导致临床结局各异的免疫机制仍不清楚。本研究调查了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局的关联。

方法

在这项前瞻性病例对照研究中，对57例GBS患者和57例年龄及性别匹配的健康对照者（HCs）进行了调查。分别使用流式细胞术、Luminex检测法和比浊法测量CD4CD25FoxP3 Treg百分比、细胞因子产生（IL-10、TNF-α、IFN-γ和IL-12）以及血清C3水平。治疗反应定义为在评估期间GBS残疾评分改善≥1分。

结果

与HCs相比，GBS患者的CD4CD25FoxP3 Tregs频率较低（p = 0.006），在急性期，其与血清C3水平呈负相关（p = 0.003）。发病后4周，C3水平正常（90 - 180mg/dL）的患者与急性GBS患者相比，Treg频率较高（p = 0.005），而C3水平持续升高的患者Treg百分比降低（p = 0.009）。在接受IVIg治疗的患者中，治疗后2周和4周Tregs显著增加，同时在4周时IL-10水平显著升高，TNF-α、IFN-γ和IL-12水平降低。然而，接受支持治疗的患者Tregs和细胞因子水平没有此类变化。此外，对IVIg有反应的患者在2周和4周时Tregs显著升高（p < 0.05），但无反应或接受支持治疗的患者则不然。