Causes and Risk Factors of Autoimmune Disease

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Autoimmune disease is a term used to describe more than 100 disorders in which your body's immune system attacks its own cells and tissues, including Hashimoto's thyroiditis, Graves' disease, type 1 diabetes, and rheumatoid arthritis. While each of the many types is unique in its disease mechanism, they all ultimately represent an immune system gone awry. Though scientists are not entirely sure what causes autoimmune diseases, the bulk of evidence suggests that genetics plays a central role in combination with external factors such as environment, lifestyle, and even past infections.

Genetics

Under normal circumstances, the immune system produces immune proteins known as antibodies every time it is exposed to a foreign agent, such as a virus or bacteria. Each antibody is programmed to kill a specific agent. If the foreign agent returns, the immune system "remembers" it and launches a repeat attack with the same antibody.

Scientists know that genetics play a part in autoimmune diseases for three reasons:

  • A great many of autoimmune diseases run in families.
  • A large number of diseases affect specific ethnic populations.
  • Genomic research has revealed specific genetic mutations common to people with different autoimmune diseases.

Some of the genetic underpinnings are clearer than others. For instance, a child's risk of multiple sclerosis (MS), a disease linked to the HLA-DRB1 mutation, increases from 0.1 percent in the general population to 2 percent—a 20-fold increase—if one of his or her parents have MS. Other diseases, like psoriasis, can affect extended family members and not just immediate ones.

We also see genetic patterns among ethnic groups, which suggests an autosomal recessive pattern of inheritance. These include type 1 diabetes, which is more common in whites, and lupus, which tends to be more severe in African-Americans and Hispanic populations.

Overlapping Genetic Causes

While the patterns of inheritance often appear specific to certain mutations, there is evidence that a shared underlying factor, most likely chromosomal, can predispose a person to autoimmunity. It is why someone with lupus will often report having family members with rheumatoid arthritis, Hashimoto's thyroiditis, or other autoimmune disorders unrelated to lupus.

At the same time, it is not uncommon for a person to have multiple autoimmune diseases, known any polyautoimmmunity. If someone has more than three, the condition is classified as multiple autoimmune syndrome (MAS).

Takeaway:

Research from the Centers for Rheumatic Diseases in Bucharest suggests that as many as 25 percent of people with an autoimmune disease will experience additional autoimmune disorders.

Some autoimmune diseases carry an increased likelihood of MAS, including rheumatoid arthritis, multiple sclerosis, Hashimoto's thyroiditis, and Sjögren’s syndrome. Other diseases are known to frequently co-occur, such as type 1 diabetes and celiac disease, both of which share mutations of the HLA-DRB1, HLA-DQA1, and HLA-DQB1 genes.

What this suggests is that a person genetically predisposed to autoimmunity may only develop a disease if exposed to an environmental trigger that effectively "switches on" the condition.

Environment and Lifestyle

While experts have gained greater insight into the genetic causes of autoimmune disease, they still remain largely in the dark about how certain environmental factors contribute. For this, they rely on epidemiological evidence to describe how certain non-genetic factors increase the risk of certain disorders, both directly and indirectly.

Despite the lack of understanding about the environmental causes of autoimmune disease, the current body of evidence suggests that they may play a bigger role than first imagined.



Takeaway:

According to research from the Scripps Institute in Los Angeles, environmental causes may account for as many as 70 percent of all autoimmune diseases.

The causes are broadly described as being related to one of three things:

  • Infections, like the Epstein-Barr virus
  • Toxic chemicals, like cigarette smoke
  • Dietary factors, like excessive salt

The researchers propose that exposure to some of these factors can interfere with the normal functioning of the immune system, potentially causing the body to respond by producing defensive antibodies.

Depending on the trigger, some antibodies are less able to differentiate between the causal agent and normal cells of the body. If this happens, the antibodies can start to damage normal tissues, thereby instigating a secondary response in which autoantibodies are produced to attack the tissues that it now considers foreign.

Examples of Environmental Triggers

This has been noted with the Epstein-Barr virus (EBV) and rheumatoid arthritis. Not only are EBV-induced antibodies higher in people with RA, but they also target and attack the same types of protein found on the surface of the virus and joint tissues. This suggests that EBV may instigate autoimmunity simply as a result of "mistaken identity" and inadvertently give rise to RA-specific autoantibodies like rheumatoid factor (RF).



Takeaway:

In addition to rheumatoid arthritis, the Epstein-Barr virus is closely linked to multiple sclerosis, inflammatory bowel disease, type 1 diabetes, juvenile idiopathic arthritis, and celiac disease.

Smoking is similarly linked to rheumatoid arthritis, lupus, multiple sclerosis, and Graves' disease, while salt is believed to alter the gut microbiota and increase the risk of type 1 diabetes and multiple sclerosis. Obesity places you at risk of both rheumatoid arthritis and psoriatic arthritis.

More research needs to be done to clarify which environmental factors pose the greatest risk to which populations and what co-factors work in tandem to create the "perfect storm" for autoimmunity.

Risk Factors

It is difficult to suggest which risk factors place you at the greatest risk of an autoimmune disease. In some cases, you are simply predisposed at birth. At other times, the disease may be caused by conditions you cannot control, like EBV infections which affect around 65 percent of the population.

However, if you have a family history of an autoimmune disease, making healthy lifestyle choices, like avoiding cigarettes and maintaining a healthy weight, may potentially reduce your risk.

If you're concerned about family history, you can ask your doctor about undergoing a panel of screening tests: the antinuclear antibodies (ANA) test and immunoglobulin IgA, IgG, and IgM tests. The results may be able to reveal your risk of certain disorders and provide you the impetus to seek further testing or take preventive measures.

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Article Sources
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  • Cojocaru, M.; Cojocaru, I. and Silosi, I. Multiple autoimmune syndrome. Maedica (Buchar). 2010;5(2):132–34.

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