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. 2022 Jul;29(7):2074-2083.
doi: 10.1111/ene.15334. Epub 2022 Apr 12.

Role of altered IL-33/ST2 immune axis in the immunobiology of Guillain-Barré syndrome

Praveen P Sharma  1 , Doniparthi V Seshagiri  1 , Madhu Nagappa  1 , Thrinath Mullapudi  2 , Nikhitha Sreenivas  2 , Saikat Dey  2 , Sumanth Shivaram  1 , Rahul Wahatule  1 , Vijay Kumawat  3 , Binu V Sreekumaran Nair  4 , Sriganesh Kamath  5 , Sanjib Sinha  1 , Arun B Taly  1 , Monojit Debnath  2
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Role of altered IL-33/ST2 immune axis in the immunobiology of Guillain-Barré syndrome

Praveen P Sharma et al. Eur J Neurol. 2022 Jul.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Guillain-Barré syndrome; IL-33; autoimmunity; inflammation; sST2.

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References

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