High Lipid Levels Associated with Increased Disability, Inflammation in RRMS Patients, Study Shows

High levels of certain lipids, or fat, in the blood are linked to increased disability scores and high levels of pro-inflammatory markers in relapsing-remitting multiple sclerosis (RRMS) patients, a small study reports.

The study, “Lipoprotein markers associated with disability from multiple sclerosis,” was published in the journal Scientific Reports.

Autoimmune diseases, including multiple sclerosis (MS), are characterized by an imbalanced immune response often accompanied by other alterations, such as changes in the metabolism of lipids.

Several studies have suggested an association between increased levels of lipids in the blood and higher MS disease activity, shown by new lesions in magnetic resonance imaging or worsening on the Expanded Disability Status Scale (EDSS), a tool used to quantify disability in MS patients.

A team of researchers at Imperial College London have now investigated the association between MS and the concentration of lipids in the blood in RRMS patients, compared with healthy volunteers. Additionally, they investigated how the levels of blood lipids correlated with markers of inflammation.

In total, they analyzed blood samples from 27 RRMS patients, who had a median EDSS score of 1.5, ranging from one (no significant disability) to seven (severe disability, essentially restricted to a wheelchair), and 31 healthy controls.

Patients had not received treatment with disease-modifying therapies or steroids for at least three months, and were relapse-free for at least one month before enrolling in the study.

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Lipids are transported in the blood in complex aggregates of proteins and lipids, called lipoproteins. Lipoproteins thus contain a mixture of lipids — triglycerides, cholesterol, and phospholipids — and proteins.

The more lipids a lipoprotein contains relative to the protein load, the lower its density. This is used as a way to divide lipoproteins into four main groups: chylomicrons, very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL).

Chylomicrons and VLDL deliver triglycerides to the cells in the body. LDL and HDL lipoproteins carry cholesterol — the function of LDL is to deliver cholesterol to cells where it is used to make membranes, for example; in contrast, HDL is used to remove excess cholesterol in the body by taking the cholesterol to the liver to be eliminated.

For these reasons, LDL is commonly known as the “bad” cholesterol and HDL as the “good” cholesterol.

Researchers analyzed blood samples of both RRMS patients and healthy controls looking at the VLDL and HDL fractions separately.

They found that the lipid content within VLDL and HDL lipoproteins is higher in MS patients than in healthy subjects, with RRMS patients having a higher concentration of 23 different lipids. Of these 23 lipids, 13 were 1.3 times higher than in healthy volunteers.

Researchers also found that lipids in the VLDL-2 fraction, namely cholesterol and free cholesterol, correlated with EDSS disability scores in RRMS patients, meaning the higher their concentration, the worse the disability score.

Moreover, free cholesterol in the VLDL-2 fraction was highly correlated with the levels of signaling molecules (cytokines), namely the chemokine (C-C motif) ligand 17 and interleukin-17, two cytokines know to be involved in inflammation.

“We have provided evidence that specific lipid concentrations within VLDL sub-fractions are correlated both with disability in RRMS patients and with pro-inflammatory plasma cytokine levels,” the researchers wrote.

These findings “suggest that clinical benefits of lipid lowering drugs with inflammatory diseases may be realized by decreasing plasma lipid concentrations,” they concluded.