Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.
Department of Human Genetics, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.
Eur J Neurol. 2022 Jul;29(7):2074-2083. doi: 10.1111/ene.15334. Epub 2022 Apr 12.
The IL-33/ST2 immune axis plays crucial roles in infection and immunity. A dysregulated IL-33/ST2 axis can induce autoimmune reaction and inflammatory responses. Guillain-Barré syndrome (GBS) is an acute peripheral neuropathy, mostly caused by post-infection autoimmunity. The role of IL-33/ST2 axis is not known in GBS. This study aimed to explore the role of IL-33/ST2 axis in GBS.
Three single nucleotide polymorphisms (SNPs) of Il33 gene (rs16924159, rs7044343, rs1342336) and three SNPs of Il1rl1 gene (rs10192157, rs1041973, rs10206753) coding for suppressor of tumorigenicity 2 (ST2) were genotyped in 179 GBS patients and 186 healthy controls by TaqMan Allelic Discrimination Assay. Plasma levels of IL-33 and sST2 were measured in a subset of GBS patients (n = 80) and healthy controls (n = 80) by ELISA.
The frequencies of CC genotype of rs10192157 (p = 0.043) and TT genotype of rs10206753 (p = 0.036) SNPs of Il1rl1 gene differed significantly between GBS patients and healthy controls. Gene-gene interaction between Il33 and Il1rl1 genes also conferred significant risk for GBS. In addition, the plasma sST2 levels were significantly elevated in GBS patients compared to healthy subjects (24,934.31 ± 1.81 pg/ml vs. 12,518.97 ± 1.51 pg/ml, p < 0.001). Plasma sST2 levels showed a significant correlation with the disability scores at the peak of neurological deficit in GBS patients.
The IL-33/ST2 axis is suggested to influence the immunopathogenesis of GBS. Genetic variants of Il1rl1 gene might serve as a risk determinant of GBS and plasma sST2 levels might emerge as a biomarker of severity of GBS, if replicated further by other studies.
IL-33/ST2 免疫轴在感染和免疫中起着至关重要的作用。失调的 IL-33/ST2 轴可诱导自身免疫反应和炎症反应。格林-巴利综合征（GBS）是一种急性周围神经病，主要由感染后自身免疫引起。IL-33/ST2 轴在 GBS 中的作用尚不清楚。本研究旨在探讨 IL-33/ST2 轴在 GBS 中的作用。
采用 TaqMan 等位基因鉴别分析，对 179 例 GBS 患者和 186 例健康对照者的 Il33 基因（rs16924159、rs7044343、rs1342336）三个单核苷酸多态性（SNP）和 Il1rl1 基因（rs10192157、rs1041973、rs10206753）三个 SNP 进行基因分型。采用 ELISA 法检测 80 例 GBS 患者和 80 例健康对照者的血浆 IL-33 和 sST2 水平。
Il1rl1 基因 rs10192157（p=0.043）CC 基因型和 rs10206753（p=0.036）TT 基因型在 GBS 患者和健康对照组之间的频率差异有统计学意义。Il33 与 Il1rl1 基因的基因-基因相互作用也显著增加了 GBS 的发病风险。此外，与健康对照组相比，GBS 患者的血浆 sST2 水平显著升高（24934.31±1.81 pg/ml vs. 12518.97±1.51 pg/ml，p<0.001）。GBS 患者血浆 sST2 水平与神经功能缺损高峰期的残疾评分呈显著相关性。
IL-33/ST2 轴可能影响 GBS 的免疫发病机制。Il1rl1 基因的遗传变异可能是 GBS 的风险决定因素，如果进一步得到其他研究的验证，血浆 sST2 水平可能成为 GBS 严重程度的标志物。
