Comprehensive cytokine profiling provides evidence for a multi-lineage Th responses in Guillain Barre Syndrome

Comprehensive cytokine profiling provides evidence for a multi-lineage Th responses in Guillain Barre Syndrome
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DOI:
10.1016/j.cyto.2018.04.026
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发表时间:
2018-10-01
期刊:
影响因子:
3.8
通讯作者:
Taly, Arun B.
Taly, Arun B.
中科院分区:
医学3区
文献类型:
--
作者:
Debnath, Monojit;Nagappa, Madhu;Taly, Arun B.

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格林巴利综合征(GBS)是最常见的获得性免疫介导的神经病变之一,通常在感染之前。虽然细胞免疫应答被证明是GBS的病理生理学的主要原因,但风险和病程的确切机制基础至今仍是个谜。细胞因子以其通过协调作用驱动细胞免疫和炎症的能力而闻名。从临床和动物模型研究中获得的数据表明,一些细胞因子在GBS的进展和恢复中具有重要意义。然而,这些研究进行了几个细胞因子和一小部分GBS患者,从而缺乏一个完整的了解的模式相关联的细胞因子代表的Th 1,Th 2和Th 17反应与GBS。我们研究了65个良好的特点GBS患者和73个年龄和性别匹配的健康对照。使用多重悬浮阵列平台测定代表Thl、Th 2和Thl 7途径的一组15种细胞因子。与健康对照受试者相比,发现GBS患者中五种细胞因子的血浆水平改变:(i)IL-1 β表现出降低的水平,和(ii)IFN-γ、IL-4、IL-21和IL-33在GBS患者中升高。本研究最重要的发现是GBS患者中IL-21和IL-33的表达上调。鉴于IL-33作为警报素的作用,该细胞因子水平的升高提供了关于细胞因子在GBS中更广泛作用的重要指示。本研究还为GBS的病理生理学中多谱系Th细胞(Th 1、Th 2和Th 17)相关的细胞因子应答提供了证据。
Guillain Barre Syndrome (GBS) is one of the commonest acquired immune-mediated neuropathies, often preceded by infections. Although cellular immune responses are shown to substantially account for the pathophysiology of GBS, the precise mechanistic basis of risk and disease course remains enigmatic till date. Cytokines are best known for their abilities to drive cellular immunity and inflammation through their co-ordinated actions. Data obtained from clinical and animal model studies suggest important implications of some of the cytokines in the progression and recovery of GBS. However, these studies were performed on few cytokines and small set of GBS patients, thereby lacking a complete understanding of the patterns of association of cytokines representing Thl, Th2, and Th17 responses with GBS.We studied 65 well-characterized GBS patients and 73 age- and sex-matched healthy controls. A panel of 15 cytokines representing Thl, Th2 and Th17 pathways was assayed using Multiplex Suspension Array platform. Plasma levels of five cytokines were found to be altered in GBS patients compared to healthy control subjects: (i) IL-1 beta exhibited reduced levels, and (ii) IFN-gamma, IL-4, IL-21 and IL-33 were elevated in GBS patients. The most important finding of this study was up-regulated expression of IL-21 and IL-33 in patients with GBS. Given the role of IL-33 as an alarmin, the elevated level of this cytokine provides important indication about a much broader role of cytokines in GBS. This study also provides evidence towards a multi-lineage Th cells (Thl, Th2 and Th17) associated cytokine responses in the pathophysiology of GBS.