Lay summary by Yasmina Ebrahim, reviewed by Dr Scott Allen & Dr Laura Evans
Background
Multiple Sclerosis (MS) is classed as an autoimmune disease; this is where a person’s own immune system attacks the coating of their own nerve cells, treating it like a threat to the body. This coating is called the myelin sheath and damage to the myelin sheath prevents nerve signals from being conducted properly; moreover, the repeated bouts of inflammation over time cause damage to the nerve cells themselves. This results in a variety of symptoms including fatigue, vision problems and difficulty walking. The reasons and mechanisms that trigger this attack are still not well-understood.
Why is the study important?
MS affects millions of people around the world, and it is the most common cause of disability in young adults. This study investigated changes in the immune system contributing to the development of the disease to shed light on what makes some people more susceptible to MS than others.
What did the authors do and how did they do it?
One of the methods that are used to aid the diagnosis of MS is the analysis of the cerebrospinal fluid (CSF), which is a fluid that surrounds the brain and the spinal cord providing support and protection. Changes in the composition of the CSF might indicate a problem affecting the brain and the spinal cord, and this is often seen with MS patients.
In this study, the researchers collected CSF from 33 patients with MS and 48 others who had other neurological disorders. They determined the numbers and types of immune cells that were present in the samples. They then examined single cells in detail to see if there were changes in how the immune cells were functioning.
If we imagine the DNA as a massive instruction book for what our cells can do, then each cell type in our body will follow a portion of these “instructions” and give “orders” to make proteins “products” that help the cells in question function properly. These “orders” are in the form of another molecule called RNA. We can use a method called single-cell RNA sequencing to see if we have normal, faulty, absent or even totally new orders being given at any one time for each of our different cell types.
In addition to the instructions stored in our DNA, we have “regulators” that control the level at which these instructions are expressed into orders (the RNA). To see how variations to these regulatory regions will affect this expression, the researchers used another method called Gene Expression Quantitative Trait Loci (eQTL) mapping.
What are the results?
The authors confirmed that the immune cells in CSF of MS patients differ in type and number. They found a rare subtype of immune cells (CD8+ T cells) that were present in higher amounts in the CSF of MS patients compared to patients with other neurological diseases. They were also able to link changes in two DNA “regulators” to different expression of some instructions the CD8+ T cells used to fight viral infections. These changes might be related to increased susceptibility in some individuals to MS.
What do the findings mean going forward for people with the disease?
There has always been a suspected link between infections with certain viruses such as Epstein–Barr virus (EBV), which causes glandular fever (infectious mononucleosis or mono), and an increased risk of developing MS. Although the study did not find any evidence of increased viral infections in people with MS compared to people with other neurological diseases, there was evidence of an altered anti-viral immune response. Understanding the underlying mechanisms that make some individuals develop an altered immune response to viral infections will help in identifying more specific disease-causing factors which could be therapeutic targets for the development of new treatments.
This study can be found at
https://doi.org/10.1093/brain/awad404
Paper title
Expression profiling of cerebrospinal fluid identifies dysregulated antiviral mechanisms in multiple sclerosis
Lead Authors
Maria Ban and, Stephen Sawcer.
Publication details including date of publication
Brain, Dec 1; 2023, Epub ahead of print.