Using Olink Proteomics to Identify Inflammatory Biomarkers in the Cerebrospinal Fluid in Guillain-Barré Syndrome

Shuanghong Sun, Meng Li,* Jihe Song,* Di Zhong Department of Neurology, The First Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Di Zhong, Department of Neurology, The First Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China, Email [email protected]: The precise etiology of Guillain-Barré syndrome (GBS) is uncertain; however, it is linked to immunological and inflammatory processes. Thus, this research aims to investigate new inflammatory biomarkers for GBS diagnosis.Patients and Methods: In this work, Olink proteomics was used to compare the expression levels of 92 inflammation-related proteins in the cerebrospinal fluid (CSF) of patients with non-inflammatory neurological diseases (n=14) and GBS (n=23). Differentially expressed proteins (DEPs) were then analyzed biologically and in terms of their relationship to clinical features, and logistic regression models were built. We also downloaded GEO data to validate DEPs at the mRNA level.Results: We identified twenty DEPs. The PPI network screened six key DEPs (including TNF, CCL20, IL8, MCP-1, IL10, and IL5). These DEPs were enriched in the chemokine signaling pathway, the IL-17 signaling pathway, cytokines and their receptor interactions, and other pathways. TNFRSF9 and IL-10RB showed the strongest correlation of expression in CSF. CCL20 and IL5 could be used as potential independent predictors for the diagnosis of GBS. Seven DEPs (MCP-1, CXCL1, MCP-4, MMP-10, CXCL10, CCL28, and CCL20) had some predictive value for the severity of GBS. Based on the validation of the GEO data, the mRNA expression of MCP-1 and CXCL9 was found to be upregulated at the peak of EAN, and the enriched pathways at the gene transcription level were consistent with the results of this study.Conclusion: DEPs linked to inflammation (such as TNF, CCL20, IL8, MCP-1, IL10, and IL5) could be useful biomarkers for GBS diagnosis. More research is required to determine their precise mechanisms in GBS. Keywords: Guillain-Barré syndrome, inflammation, biomarkers, olink proteomics, bioinformatics analysis