Multiple sclerosis (MS) is widely regarded as an autoimmune disease — a condition in which the immune system mistakenly attacks the body’s healthy cells. In MS, this results in damage to the myelin, the protective covering of nerve fibers. While most experts agree that the immune system plays a key role in the development of MS, some still question whether it fully fits the definition of an autoimmune disease.

In this article, we’ll explore why some health care professionals believe MS might not be classified as an autoimmune disorder and look at which aspects of the disease are linked to autoimmunity.

What Is the Argument Against MS as an Autoimmune Disease?

A condition must meet several criteria to be classified as an autoimmune disease. One important factor is that the immune system attacks a specific substance in the body, called an autoantigen, found in everyone with the condition.

Much of the argument against MS as an autoimmune disease relates to the autoantigens associated with the disease. Antigens are substances recognized by the immune system as an invader or foreign. An autoantigen (or self-antigen) refers to a substance from the body’s own cells and tissues that the immune system mistakenly targets.

Scientists can measure the immune response to an autoantigen by checking if certain immune cells specifically recognize it. The cells they usually look at include B cells and T cells. To see if a T cell reacts to an autoantigen, scientists analyze its T-cell receptor (TCR). The TCR is a part of the T cell that binds to antigens and autoantigens. It also helps activate the T cell, triggering it to start fighting infections or other targets in the body.

For B cells, scientists will look for an autoantibody in the blood and cerebrospinal fluid in the spinal canal. These autoantibodies are produced and released by B cells, and they attach to autoantigens.

Many autoantigens linked to MS have been identified for T cells and B cells. These include molecules called myelin basic protein, proteolipid protein, and myelin oligodendrocyte glycoprotein. These autoantigens come from the protective myelin sheath that covers nerve fibers in the central nervous system (CNS). They can also be found in other cell types in the CNS, including neurons, astrocytes, and oligodendrocytes.

Scientists and neurologists don’t always find the same pattern of immune response among people living with MS. This information creates the argument against MS being classified as an autoimmune disease. It also influences some people to refer to it as an immune-mediated disease instead.

Is There Evidence That MS Is Autoimmune?

Although a universal autoantigen has not been identified for MS, many components of the disease still suggest an autoimmune basis. Evidence for the autoimmune activity in MS also implies that it is an immune-mediated disease. This evidence relates to:

• Genetic and environmental risk factors
• Immune system activity in MS
• Immune-modulating therapies for MS

Genetic and Environmental Risk Factors

The exact cause of MS is unknown. However, scientists and epidemiologists (scientists who study how diseases spread) have mentioned some environmental and genetic risk factors associated with developing the disease. Many of these factors are associated with the immune system. For example, a person with a particular version of a gene called HLA-DRB1*15:01 is three times more likely to develop MS. This gene is important for activating T cells in the immune system.

Environmental factors, such as infection with certain viruses, also put a person at a higher risk of developing MS. It’s thought that these infections might activate the immune system to begin attacking the body’s tissues. Although we don’t yet know how these infections activate the immune system to attack the body, scientists believe this may play a role in how MS develops.

Immune System Activity in MS

Scientists have isolated B cells and T cells from people with MS that specifically react to autoantigens. Additionally, they have detected autoantibodies in the blood of those with the condition. When scientists analyze the function of the immune cells of people living with MS, the cells are often dysfunctional.

For example, a type of T cell called a regulatory T cell is meant to suppress the immune system and prevent it from attacking the body by mistake. Studies have shown that these regulatory T cells are dysfunctional in MS, failing to adequately suppress immune activity.

Scientists have also found T cells, B cells, and another immune cell type, called a macrophage, in active lesions in the brain and spinal cord. This finding suggests that these immune cells might be involved in the damage that happens in the CNS during an MS attack.

Immune-Modulating Therapies for MS

Many MS treatments work by suppressing the immune system or by preventing it from attacking the CNS. This includes corticosteroids (steroids), which can suppress inflammation and immune cell activity. Corticosteroids are usually given right away when symptoms start to get worse during a flare or a relapse.

Therapies that deplete immune cells, such as B cells, with ocrelizumab (Ocrevus) have also been effective. Rituximab (Rituxan) is another example of a medication for MS that specifically targets the immune system. Suppressing the immune system during an MS flare helps improve disease outcomes, which provides additional evidence that the immune system is involved in the development of MS.

Understanding the Immune System and MS

MS is a disease in which the immune system attacks the CNS, causing damage to the protective covering of nerve cells, known as demyelination. This damage leads to symptoms associated with the disease. Some people debate whether the diagnosis of MS is a true autoimmune disease. However, the dysfunction of the immune system during this condition is clear, and the immune system certainly plays a role.

As technology advances for screening and identifying B cells and T cells reactive against autoantigens, scientists may identify the universal autoantigen associated with MS. Nonetheless, the characteristics of MS strongly indicate that it is an immune-mediated disease.

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