Causes of MS

Multiple sclerosis (MS) is an autoimmune disease characterized by inflammation and damage to the myelin sheath in cells of the central nervous system, composed of the brain and spinal cord.

The immune system defends the body against foreign invaders, such as viruses and bacteria. Simplistically, its job is to attack anything that looks like it could cause injury or disease, while leaving the body’s healthy tissue alone. In autoimmune diseases like MS, however, the immune system erroneously recognizes the body’s own cells as a foreign threat, and launches an inflammatory attack against those cells.

In people with MS, the immune system attacks the myelin sheath, a fatty substance that surrounds and protects neurons, or nerve cells. This sheath is important for neurons to effectively send electrical signals, a bit like insulation wrapped around a metal wire. The loss of the myelin sheath leads to nerve cell degeneration, and a range of disease symptoms.

The myelin sheath is produced by cells called oligodendrocytes. These cells are normally able to remyelinate nerve fibers — meaning, wrap them in a new myelin sheath — but the repeated immune attacks against myelin lead to less and less effective remyelination and the eventual formation of scar-like lesions.

As is the case with most autoimmune diseases, the exact cause of MS is not known. Several types of immune cells, including B-cells and T-cells, are thought to participate in the autoimmune attack.

Multiple factors likely contribute to the development and progression of MS. It is probable that both genetic and environmental factors play a role, scientists say.

Genetics

MS is not a heritable disease, though about one in eight patients have a family history of the neurodegenerative disorder. Genetic factors may predispose people to the disease, either alone or in combination with other factors. Some 200 genes are thought to possibly contribute — even in small ways — to MS development.

A variant, or mutation, in a gene involved in the immune system, called HLA-DRB1, is thought to be the strongest genetic risk factor for this disease, although the mechanism underlying it is not known.

Geography

MS is more prevalent in some geographical regions than others, with the highest disease prevalence found in countries of northern Europe, and throughout the northern U.S., southern Canada, New Zealand, and southern Australia. The distance a person lives from the equator seems to correlate with a risk of developing MS, with more patients identified in regions that are farther from the equator.

Notably, variations in geographic risk are thought to be the result of environmental factors, not genetics: adults from low-risk countries who migrate to Europe are still at a relatively low risk of developing MS, but children born to migrants in Europe are at a high risk of MS.

Vitamin D

Vitamin D, which helps regulate the amount of calcium and phosphate in the body, is important for immune system health. There appears to be a link between vitamin D deficiency and an increased chance of developing MS. This deficiency also could explain differences in disease prevalence by geographic location — people living closer to the equator are more exposed to sunlight year-round, so their bodies produce more vitamin D.

Smoking

Smoking is linked to an increased risk of developing MS, and evidence suggests that patients who are current or former smokers tend to develop more rapidly progressing forms of the disease.

Biological sex

MS is about three times as common among females as it is in males. In general, women are more likely to develop autoimmune diseases. The reason for this difference likely has to do with hormonal and chromosomal differences among the sexes.

Obesity

People who are obese in childhood and adolescence are at increased risk of MS later in life. The link is particularly strong in girls. Obesity is thought to contribute to MS because it promotes chronic low-grade inflammation, which can affect immune responses.

Infections

Some infections have been linked to MS, particularly the Epstein-Barr virus (EBV), which causes infectious mononucleosis (often abbreviated as “mono”). People who are truly negative for EBV are at a lower-than-normal risk of developing MS, while for people with symptomatic EBV infections, the risk of developing the disease is more than doubled.

EBV infections have been proposed to be a root cause of MS, since virtually all MS patients have been infected with the virus at some point in their lives. Researchers believe that the virus is able to mislead the immune system into developing antibodies against the myelin sheath.

 

Last Updated: June 15, 2021

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