MS metabolic profile for MS. Closer to a blood test.

[frodo]

Metabolome-based signature of disease pathology in MS

https://www.sciencedirect.com/science/a ... 4819301117

Highlights

• Six serum metabolites were predictive for MS in males.
• Results support lipidomic changes in MS.
• Several MS risk variants were associated with the top predictive metabolites.
• Pathways analyses suggest processes involved in MS pathology.


Background

Diagnostic delays are common for multiple sclerosis (MS) since diagnosis typically depends on the presentation of nonspecific clinical symptoms together with radiologically-determined central nervous system (CNS) lesions. It is important to reduce diagnostic delays as earlier initiation of disease modifying therapies mitigates long-term disability. Developing a metabolomic blood-based MS biomarker is attractive, but prior efforts have largely focused on specific subsets of metabolite classes or analytical platforms. Thus, there are opportunities to interrogate metabolite profiles using more expansive and comprehensive approaches for developing MS biomarkers and for advancing our understanding of MS pathogenesis.
Methods

To identify putative blood-based MS biomarkers, we comprehensively interrogated the metabolite profiles in 12 non-Hispanic white, non-smoking, male MS cases who were drug naïve for 3 months prior to biospecimen collection and 13 non-Hispanic white, non-smoking male controls who were frequency matched to cases by age and body mass index. We performed untargeted two-dimensional gas chromatography and time-of-flight mass spectrometry (GCxGC-TOFMS) and targeted lipidomic and amino acid analysis on serum. 325 metabolites met quality control and supervised machine learning was used to identify metabolites most informative for MS status. The discrimination potential of these select metabolites were assessed using receiver operator characteristic curves based on logistic models; top candidate metabolites were defined as having area under the curves (AUC) >80%. The associations between whole-genome expression data and the top candidate metabolites were examined, followed by pathway enrichment analyses. Similar associations were examined for 175 putative MS risk variants and the top candidate metabolites.
Results

12 metabolites were determined to be informative for MS status, of which 6 had AUCs >80%: pyroglutamate, laurate, acylcarnitine C14:1, N-methylmaleimide, and 2 phosphatidylcholines (PC ae 40:5, PC ae 42:5). These metabolites participate in glutathione metabolism, fatty acid metabolism/oxidation, cellular membrane composition, and transient receptor potential channel signaling. Pathway analyses based on the gene expression association for each metabolite suggested enrichment for pathways associated with apoptosis and mitochondrial dysfunction. Interestingly, the predominant MS genetic risk allele HLA-DRB1×15:01 was associated with one of the 6 top metabolites.
Conclusion

Our analysis represents the most comprehensive description of metabolic changes associated with MS in serum, to date, with the inclusion of genomic and genetic information. We identified atypical metabolic processes that differed between MS patients and controls, which may enable the development of biological targets for diagnosis and treatment.

[frodo]

And here other report about another possible blood test. By the way, TWEAK is this:

https://en.wikipedia.org/wiki/TNFSF12

Interestingly, related to angiogenesis too.

Here comes the report:

High levels of soluble serum TWEAK are associated with neuro inflammation during multiple sclerosis

https://www.ms-uk.org/high-levels-solub ... -sclerosis

Inflammation and demyelination are the main processes in multiple sclerosis (MS). However, to date, blood biomarkers of inflammation are lacking. TWEAK, a transmembrane protein that belongs to the TNF ligand family, has been previously identified as a potential candidate.

A study, published in the Journal of Translational Medicine, recruited 28 patients (9 males and 19 females). They were prospectively included after a first clinical episode suggestive of MS and clinically followed for three years. Fifty-seven healthy controls were also included. TWEAK serum levels and MRI exams including magnetisation transfer imaging were performed at the beginning of the study, and then at 6- and 12-months to follow up.

The results showed that TWEAK serum levels were significantly increased in the patient group compared to healthy controls. Serum levels of soluble TWEAK were significantly increased during relapses, compared to time periods without any relapse. Moreover, patients presenting at least one gadolinium-enhanced central nervous system lesion at baseline displayed significantly increased serum TWEAK levels in comparison with patients without any gadolinium-enhanced lesion at baseline. No correlation was evidenced between TWEAK serum levels and the extent of brain tissue damage assessed by magnetisation transfer ratio.

The researchers concluded that the present study showed TWEAK serum levels are increased in MS patients, in relation to disease activity. ‘This simple and reproducible serum test could be used as a marker of ongoing inflammation, contributing in the follow-up and the care of MS patients. TWEAK is a promising serum marker of the best window to perform brain MRI, optimising the disease control in patients,’ they claimed.