What triggers the immune response against myelin in MS?

29 March 2023

  • Myelin is the fatty coating around nerves that is mistakenly attacked by the immune system in MS.
  • MS Australia-funded researchers found that subtly changing the fats in the myelin sheath was enough to destabilise myelin and cause brain inflammation in a laboratory model.
  • Understanding triggers of immune attack on myelin is a critical step in understanding how MS develops and how to treat myelin damage in MS.

The myelin sheath is the fatty coating around nerves in the brain and spinal cord that enables efficient nerve conduction.

In multiple sclerosis (MS), immune cells mistakenly attack and damage the myelin sheath. This disrupts nerve conduction and can result in many different neurological symptoms, depending on which part of the brain or spinal cord is affected.

We don’t yet understand what triggers this immune attack on the brain and spinal cord.

What was the aim of the research?

To help understand what triggers brain autoimmunity in MS, Associate Professor Anthony Don‘s team focused on studying the structure of the myelin, and how the immune system is activated when myelin is compromised.

In humans, 25-35% of the fats in myelin are “sphingolipids” made by enzymes in the myelin-producing cells. Specific sphingolipids, called sulfatide and galactoceramide, are unique to myelin and determine its stability.

In a new MS Australia-funded study, the team investigated the effect of subtly changing these sphingolipids in the myelin, to examine whether this could trigger an autoimmune attack on the brain.

What did the researchers do?

Using a laboratory model, researchers blocked one of the enzymes responsible for producing the myelin sphingolipids, galactoceramide and sulfatide.

By blocking the enzyme, the researchers were able to create myelin with slightly shorter sphingolipids compared to the normal sulfatide and galactoceramide.

What did the researchers find?

Changing the sphingolipid length had several consequences. The myelin sheath was thinner, and fewer nerve cells were myelin-coated.

The researchers also found that the immune system was activated very early on in the brain and increased over time. A specific type of immune cell called “microglia”, which has the capacity to attack myelin, was activated. Over time, the myelin became damaged, causing neurological symptoms to develop.

In addition to the effects on myelin thickness and immune system activation, the team also found that changing the sphingolipids resulted in damage to other myelin sheath proteins, such as “myelin basic protein (MBP)”.

MBP is believed to be another target of autoimmunity in MS. These findings suggest that sphingolipids play an important role in the overall integrity of myelin.

What does this mean for people with MS?

This study has provided important new insights into the triggers and molecules involved in the immune sensing of compromised myelin. This is critical for our understanding of how MS develops.

The hope is that these studies will help to support the development of new therapies to prevent and repair myelin damage in people with MS.


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What triggers the immune response against myelin in MS?