Levels of fat molecules in blood can affect relapses, disability in children

Alterations in the levels of certain fat molecules in the bloodstream are significantly associated with a higher risk of relapse and a poorer disability status in children and adolescents with multiple sclerosis (MS), according to a recent study.

It’s not yet clear if such alterations contribute to the inflammation and neurodegeneration that mark the disease, or if they are a consequence of disease-related changes.

“Lipid [fat] metabolites should be further investigated as biomarkers of disease activity and severity, as findings could lead to identifying new therapeutic targets,” the researchers wrote.

The study, “Several serum lipid metabolites are associated with relapse risk in pediatric-onset multiple sclerosis,” was published in the Multiple Sclerosis Journal.

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Lipids are key component of myelin and can affect neuroinflammation

In MS, the immune system mistakenly attacks the myelin sheath, a fatty substance that surrounds nerve cells, resulting in inflammation, nerve damage, and the onset of disease symptoms.

Metabolic alterations have been reported in both adult and pediatric MS populations compared with healthy controls. However, whether specific metabolites — the products of the cellular metabolism — have prognostic value remains largely unexplored.

Researchers at the University of California, San Francisco, and Johns Hopkins University focused on the products of the lipid metabolism. These may have a particular relevance, as lipids are a key component of myelin and can play a role in neuroinflammation.

Blood samples from 61 children either with pediatric-onset MS or clinically isolated syndrome and considered at risk of MS were examined to understand whether changes in blood lipid metabolites affect disease relapses or disability. Their median time since disease onset was less than one year.

“While relatively rare, pediatric-onset MS (POMS) can serve as a unique platform to investigate lipid’s role in the disease course,” the researchers wrote. “The limited exposure to environmental and other confounding factors, such as comorbidities, along with the higher relapse rates in this group may provide better insight into disease mechanisms.”

Boys were the majority of this group (55%), which had a mean age of 14.6 years. Most were white (51%) and were using disease-modifying therapies (DMTs) to slow progression and prevent relapses (74%).

Over a median follow-up of 2.8 years, a median of one relapse was reported for each child.

Researchers examined whether individual lipid metabolites linked with the number of relapses during follow-up, as well as disability status at the time of enrollment, as measured with the Expanded Disability Status Scale (EDSS). Findings were adjusted for factors such as age, sex, race, DMT use, and vitamin D levels to minimize the impact of those factors.

Both relapse rates and EDSS scores are “important, and relevant clinical outcomes  in MS,” the researchers noted.

Significant links between lipid metabolites, disease status in children with MS

Results showed acylcarnitines and polyunsaturated fatty acids (PUFAs) are both associated with a higher relapse risk and greater disability at the study’s start. Acylcarnitines are important metabolites in cellular energy pathways, while PUFAs have been linked with neuroinflammation.

Other lipid metabolites — namely, ceramides, sphingolipid metabolites, monoacylglycerols, and diacylglycerols — were associated significantly with worsening disability scores alone. Monohydroxy fatty acids were linked only with a higher risk of relapses.

Some lipids examined appear to have a protective role. For example, phosphatidylethanolamines (PE), plasmalogens, and primary bile acids all significantly associated with a lower risk of relapse and lower disability scores.

PEs, a component of the cell’s membranes, also can modulate the immune response, while plasmalogens are highly abundant in the nervous system, where they have a structural role and exert antioxidant and neuroprotective properties.

Overall, this study “in pediatric MS suggests several lipid pathways may be associated with MS activity and disability,” the researchers wrote.

“These lipid metabolites may have a direct detrimental role in the inflammatory and neurodegenerative mechanisms,” the team added. “They can also be a consequence and downstream effect of the pathological changes occurring in the disease (myelin degradation and axonal injury) or be part of a compensatory, protective effort in the body.”

Limitations to the study included blood samples collected after a child’s diagnosis, when changes could have been made to diets, and the lack of data about body mass index (a measure of body fat) and MRI activity. Further studies will be needed to confirm the findings and identify potential biomarkers of disease prognosis, the scientists wrote.