Potential biomarkers identified by tandem mass tags based quantitative proteomics for diagnosis and classification of Guillain–Barré syndrome

Abstract

Background and purpose: Guillain-Barré syndrome (GBS) is an acute inflammatory autoimmune and demyelinating disease of the peripheral nervous system. Currently, valid biomarkers are unavailable for the diagnosis of GBS.Methods: A comparative proteomics analysis was performed on the cerebrospinal fluid (CSF) from 10 patients with GBS and 10 patients with noninflammatory neurological disease (NND) using the tandem mass tags technique. The differentially expressed proteins were analyzed by bioinformatics, and then the candidate proteins were validated by the enzyme-linked immunosorbent assay method in another cohort containing 160 samples (paired CSF and plasma of 40 patients with GBS, CSF of 40 NND patients and plasma of 40 healthy individuals).Results: In all, 298 proteins were successfully identified in the CSF samples, of which 97 differentially expressed proteins were identified in the GBS and NND groups. Three key molecules were identified as candidate molecules for further validation. The CSF levels of TGOLN2 and NCAM1 decreased in GBS patients compared with NND patients, whereas the CSF levels of APOC3 increased. The enzyme-linked immunosorbent assay results were consistent with our proteomics analysis. Interestingly, in the validation cohort, serum APOC3 levels in the GBS group were consistent with those in the CSF samples and significantly higher than those in the healthy control group. Conclusions:Our preliminary data suggest that the CSF protein expression profile of patients with GBS is different from that of patients with NND. Moreover, alterations of TGOLN2, NCAM1and APOC3 may be used as novel biomarkers for identifying patients with GBS.

The analysis of serum lipids profile in Guillain-Barre syndrome

“…In a previous study, significantly higher levels of APOC3 were detected in the CSF and serum of GBS patients compared to other neurological diseases and healthy control groups (5). Similarly, current analysis revealed elevated expression of APOC3 in severe GBS cases and GBS patients with positive CSF neurovirus IgG.…”

“…In our previous study investigating proteomic differences between the cerebrospinal fluid (CSF) samples of GBS patients and the control group, we observed that the identified proteins were primarily enriched in pathways associated with lipid metabolism (5). Additionally, our study revealed significantly higher expression of APOC3 in the CSF and serum of GBS patients compared to other neurological disease groups and healthy individuals undergoing physical examination (5). A recent investigation demonstrated that APOC3 induces the activation of the NLRP3 through Caspase8 and TLR2/4, leading to the release of interleukins and amplification of the inflammatory response (6).…”

Remnant Cholesterol and Dyslipidemia Are Risk Factors for Guillain–Barré Syndrome and Severe Guillain–Barré Syndrome by Promoting Monocyte Activation

“…It is of great importance to explore the risk factors for GBS disease and severe GBS. In our previous study on the proteomics differences between the CSF samples of GBS patients and the control group, it was found that the differential proteins were mainly enriched in lipid metabolism-related pathways ( 5 ). In this study, we explored the potential risk factors for GBS and severe GBS, taking serum lipid factors into account.…”

“…There have been many studies on the clinical epidemiology of GBS, but its cause is not completely clear. A proteomics study of the cerebrospinal fluid of GBS patients showed that the differentially expressed proteins between the GBS and control groups were mainly enriched in pathways closely related to lipid metabolism ( 5 ). It is interesting that the concept of cholesterol toxicity was proposed.…”

Apolipoprotein C3: form begets function

“…There are several emerging links between APOC3 and inflammation, some of which are associated with APOC3’s regulation of triglycerides and cholesterol and others that are not. Serum APOC3 levels can be elevated in states of inflammation, including the autoinflammatory conditions rheumatoid arthritis ( 62 ), systemic lupus erythematosus ( 63 ), and Guillain-Barré syndrome ( 64 ). In one study, patients with high APOC3 levels undergoing coronary angiography had significantly higher markers of systemic inflammation, such as high-sensitivity C-reactive protein (hsCRP) ( 65 ).…”