Serum phospholipidomics reveals altered lipid profile and promising biomarkers in multiple sclerosis

Ferreira HB, Melo T, Monteiro A, Paiva A, Domingues P, and Domingues MR. (2020) Serum phospholipidomics reveals altered lipid profile and promising biomarkers in multiple sclerosis. Archives of Biochemistry and Biophysics

Multiple sclerosis (MS) is a progressive disease of the central nervous system characterized by neurodegeneration, demyelination, and neuroinflammation. It can cause a range of symptoms including tingling, numbness, muscle weakness, muscle spasms, pronounced reflexes, difficulty moving, ataxia, visual problems, and problems with speech. MS is not completely understood, but is known to involve a reduction of myelin, the sheath that surrounds axons composed of phospholipids and proteins for insulation, protecting the electrical signal required for neurotransmission. This may occur through defects in its production or through degradation of myelin by the immune system. Myelin is composed of lipid and protein, with the phospholipids portion of myelin being largely (~70%) plasmalogens, a unique class of lipids that contain a vinyl-ether bond. Ferreira et al wanted to characterize the phospholipid profile of MS patients in comparison to control patients, and whether there is a difference depending upon disease status.

Serum samples from 30 healthy control patients and 24 MS patients were tested using hydrophilic interaction liquid chromatography-mass spectrometry (HILIC-MS) to measure phospholipid levels in the serum. Of the 161 lipids analyzed, 16 were found to be contribute the most to the group discrimination. Eight of those with the greatest differences were ether-linked phospholipids, including plasmalogens, phosphotidylethanolamines, and phosphotidylcholines all of which were decreased in the MS patients compared to the healthy controls.

Hierarchical clustering analysis (HCA) was used to identify of phospholipid species that could discriminate between individuals with MS and controls. This analysis showed a clear clustering of individual phospholipid species with 24 species found to be reduced in the MS samples, of which 11 were plasmalogens. In addition to comparing the profiles between the healthy controls and the MS patients, the patients in remission were also compared to those in relapse to determine whether disease state produces different lipidomes. Both MS group clusters were separate from the healthy control group, as expected, but were also separate from each other, indicating that there are some phospholipid differences between those that are in an MS relapse and are experiencing symptoms compared to those in remission and mostly symptom-free.

Ferriera et al have provided support for the role of plasmalogens in the pathology of MS through comparing the levels between healthy controls and patients with MS. As well, people with MS commonly go through phases of relapse and remission of the disease, where it is known that there are pathological differences. During relapse, inflammation worsens, therefore a difference in the lipidome during this phase compared to an individual in remission was expected. However, it is important to note that the two stages of the disease have some overlap of the hierarchical clustering, indicating that although symptoms may not be present during remission, there is still a significant difference in the lipidome compared to healthy controls. Characteristic of MS is the degradation of myelin and increase in oxidative stress. As plasmalogens make up a large proportion of the lipid content of myelin and are known antioxidants, it is perhaps unsurprising that the work by Ferreira et al showed their reduction. Further work looking at the lipidome in different disease states may provide a better understanding of MS pathology and the potential utility of lipids as biomarkers for clinical diagnoses.