Medicine & Pharmaceuticals

Metabolomics Identifies Biomarkers for Guillain-Barre Syndrome

The methods and solutions described here are for research use only and not for use in clinical diagnostic procedures. 

“…to our knowledge, this is the first and the most comprehensive study on integrative profiles of primary metabolites and lipids from CSF samples with GBS patients”

Guillain-Barre syndrome (GBS) is a rapid-onset autoimmune condition that attacks the peripheral nerves. It is characterised by pain and muscle weakness in the hands, feet and limbs, and can even result in even paralysis.

Rapid treatment is needed to prevent progression to a severe clinical course. However, GBS is often difficult to diagnose since it has similar symptoms to several other conditions, such as inflammatory demyelination disorders of central nervous system (IDDs).  Furthermore, specific biomarkers have not been well defined. There are different subtypes of GBS, but it is not always easy to confirm which subtype a patient has, and so which treatment would be best.

A recent metabolomic study identified biomarkers for the three most common subtypes of GBS, which should facilitate more timely diagnosis of the condition. Metabolomic analysis is a valuable tool for biomarker identification as it measures all small molecules within a cell. Consequently, no prior understanding of a process is needed.

Some molecular indicators for the different subtypes of GBS have been proposed based on metabolic studies on blood plasma. The latest metabolomic research was conducted on cerebral spinal fluid (CSF), which it was hypothesised would provide more detail since it is in direct contact with the nerves that are damaged by GBS.

Using a Bruker ASCEND III 600 spectrometer equipped with a cryoprobe, CSF samples from 86 patients with GBS and 20 healthy controls were analysed by one-dimensional 1H-Overhauser effect nuclear magnetic resonance spectroscopy (NOESY NMR). Lipidomic profiles were investigated in parallel. The results obtained were compared with those obtained previously using samples from patients with an IDD.

The concentrations of specific metabolites were shown to differ significantly between the IDDS and GBS. Levels of glucose and ketone bodies were found to be elevated in GBS but not in the IDD. In contrast, lactate was elevated in IDD but reduced in GBS.

The differences in metabolic profiles observed for three common GBS subtypes reflected known comparisons of clinical presentation. The AIDP and AMAN GBS subtypes, which have similar symptoms, had similar metabolic profiles. The clinically distinct MFS subtype of GBS showed a similar distinction from the AIDP and AMAN GBS subtypes in its metabolic profile. Depletion of creatine and lysine was unique to the MFS subtype.

Levels of particular lipids were also seen to be unique to the different subtypes of GBS.  Furthermore, a correlation was seen between the level of sphingomyelins in the CSF and the level of GBS-related disability (GBS Hughes score).

It is hoped that the unique metabolic features of primary metabolic dysfunction and aberrant lipid metabolism observed in the GBS samples studied may lead to better understanding of the underlying pathology of GBS. This in turn may lead to the development of a unique biomarker signature and new therapeutic strategy for future clinical application, which could facilitate the early and precise diagnosis of GBS so patients can receive the correct treatment earlier and benefit from improved treatment outcomes.

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Park SJ, et al. Integrative metabolomics reveals unique metabolic traits in Guillain-Barré Syndrome and its variants. Scientific Reports 2019;9:article number: 1077. https://www.nature.com/articles/s41598-018-37572-w#Sec9