Validation of elevated levels of interleukin-8 in the cerebrospinal fluid, and discovery of new biomarkers in patients with GBS and CIDP using a proximity extension assay

Front Immunol. 2023 Nov 23:14:1241199. doi: 10.3389/fimmu.2023.1241199. eCollection 2023.

Abstract

Background: Biomarkers for diagnosis of inflammatory neuropathies, assessment of prognosis, and treatment response are lacking.

Methods: CSF and EDTA plasma from patients with Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), healthy controls (HC) and disease controls were analyzed with Olink multiplex proximity extension assay (PEA) from two independent cohorts. Levels of interleukin-8 (IL8) were further analyzed with ELISA in patients with GBS, CIDP, paraproteinemia-related demyelinating polyneuropathy (PDN), multifocal motor neuropathy (MMN), HC and disease controls. ROC analysis was performed. Outcome was measured with the GBS-disability score (GBS-ds) or Inflammatory Neuropathy Cause and Treatment (INCAT) score.

Results: In CSF, multiplex PEA analysis revealed up-regulation of IL8 in GBS compared to CIDP and HC respectively, and CIDP compared to HC. In addition, levels of IL2RA were upregulated in GBS compared to both HC and CIDP, SELE in GBS compared to HC, and ITGAM, IL6, and NRP1 in GBS compared to CIDP. In plasma, levels of MMP3, THBD and ITGAM were upregulated in CIDP compared to HC. Validation of multiplex IL8 results using ELISA, revealed increased levels of IL8 in CSF in patients with GBS and CIDP versus HC and non-inflammatory polyneuropathies (NIP) respectively, as well as in PDN versus NIP and HC. Levels of IL8 in CSF correlated with impairment in the acute phase of GBS as well as outcome at 6-months follow up.

Conclusion: IL8 in CSF is validated as a diagnostic biomarker in GBS and CIDP, and a prognostic biomarker in GBS. Multiplex PEA hereby identifies several potential biomarkers in GBS and CIDP.

Keywords: Guillain-Barré syndrome; Olink proteomics; cerebrospinal fluid; chronic inflammatory demyelinating polyneuropathy; interleukin-8; multifocal motor neuropathy; paraproteinemia-related demyelinating polyneuropathy; plasma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • Enzyme-Linked Immunosorbent Assay
  • Guillain-Barre Syndrome* / cerebrospinal fluid
  • Guillain-Barre Syndrome* / diagnosis
  • Humans
  • Interleukin-8
  • Polyneuropathies*
  • Polyradiculoneuropathy, Chronic Inflammatory Demyelinating* / cerebrospinal fluid
  • Polyradiculoneuropathy, Chronic Inflammatory Demyelinating* / diagnosis

Substances

  • Biomarkers
  • Interleukin-8
  • CXCL8 protein, human

Grants and funding

IKm has received a research grant from Norlin’s foundation, The Swedish Neurological Society, and the Stockholm patient national association for neurological diseases Neuro Stockholm. MA was supported by grants provided by Region Stockholm (ALF project, 20180181), the Swedish Association for Persons with Neurological Disabilities, Karolinska Institutet funds and Foundation of Swedish MS research.