Autoimmune diseases are conditions where the immune system mistakenly attacks the body’s own healthy cells and tissues. There are over 80 different autoimmune diseases that affect a wide range of body systems and organs. Some common examples include type 1 diabetes, rheumatoid arthritis, lupus, and multiple sclerosis. The exact causes of autoimmune diseases are still not fully understood, but research has uncovered several factors that are thought to contribute to their development. This article will explore two of the leading theories on what triggers autoimmune disorders – genetic susceptibility and environmental triggers. Understanding the potential underlying causes is an important step towards developing more effective treatments and prevention strategies for these chronic and often disabling conditions.
What is an autoimmune disease?
An autoimmune disease is a condition where the immune system, which normally protects the body from foreign invaders like bacteria and viruses, mistakenly identifies the body’s own healthy cells and tissues as a threat. This causes the immune system to produce antibodies that attack the body’s own cells and tissues, leading to inflammation and damage. Normally the immune system can distinguish between “self” and “foreign” cells. But in autoimmune disease this ability to distinguish self from non-self fails and the body begins attacking its own cells and tissues as if they were foreign invaders. This leads to a variety of symptoms and illness depending on which parts of the body are under attack.
Genetic susceptibility
One leading theory is that autoimmune diseases are triggered in genetically susceptible individuals. Researchers have found that autoimmune diseases tend to run in families, indicating that genetics play a role. People with a family history of a particular autoimmune disease are at an increased risk of developing that same condition. For example, if you have a parent or sibling with rheumatoid arthritis, you are three to five times more likely to develop RA compared to someone with no family history.
Studies of twins provide further evidence that genetics contribute to autoimmune risk. Identical twins share 100% of the same genes, while non-identical (fraternal) twins share only 50% of the same genes. Research shows that if one identical twin develops an autoimmune disease like multiple sclerosis (MS), there is a 25-30% chance the other twin will also develop MS. For non-identical twins, this risk drops to only 2.5-5%.
The major histocompatibility complex (MHC) region on chromosome 6 contains many genes that code for immune proteins. Certain variations in MHC genes appear to increase susceptibility to autoimmune conditions. People who have the genetic predisposition only develop the disease when exposed to certain environmental triggers (which will be discussed next). So while genetics load the gun, something in the environment needs to pull the trigger for autoimmunity to develop.
Examples of genetic links to autoimmunity
- Rheumatoid arthritis: Certain MHC class II alleles like HLA-DRB1*04 are associated with increased RA risk.
- Multiple sclerosis: HLA-DRB1*15 allele increases MS risk.
- Type 1 diabetes: HLA-DR and HLA-DQ alleles are linked to increased T1D risk.
- Systemic lupus erythematosus: Interferon regulatory factor 5 (IRF5) gene variant increases lupus risk.
While researchers continue to identify specific genes and gene variants associated with increased susceptibility, genetics alone cannot explain everything. Even identical twins, who share the exact same genetic makeup, only have a 25-30% chance of both developing conditions like MS. This indicates environmental factors also play an important role.
Environmental triggers
The second major theory is that environmental exposures act as triggers that set off autoimmunity in genetically susceptible individuals. Potential environmental triggers include:
Infections
Certain bacterial, viral, and parasitic infections are thought to initiate autoimmunity. Infection may trigger autoimmunity through:
- Molecular mimicry – when microbial proteins are similar in structure to self-proteins.
- Epitope spreading – when cell damage from infection exposes new immune cell epitopes.
- Persistent infections causing ongoing immune stimulation.
Examples of infections linked to autoimmune conditions:
- Strep throat and rheumatic fever – antibodies target heart tissues.
- Coxsackievirus infection associated with type 1 diabetes.
- EBV infection linked to multiple sclerosis.
Gut microbiome
Changes or imbalances in the microbial environment of the intestines may promote autoimmunity through effects on immune regulation, intestinal permeability, and molecular mimicry. This gut-autoimmunity link is an emerging area of research.
Autoimmunity and High-Salt Diets
Recent research suggests that high salt intake may represent an environmental trigger for some autoimmune diseases by inducing the activation of pathogenic immune cells, particularly Th17 cells.
Th17 cells have been strongly implicated in various autoimmune diseases like multiple sclerosis and rheumatoid arthritis.
In mouse studies, increased dietary salt resulted in more severe clinical outcomes in models of autoimmunity, which was associated with increased Th17 cells. The high-salt diet seemed to act directly on the pathogenicity of the Th17 cells.
Human studies have also found associations between increased salt consumption and worsened disease activity and inflammation in autoimmune conditions. The salt may enhance existing autoinflammatory processes by increasing the activity of pathogenic Th17 cells.
However, more research is still needed to better understand the role of dietary salt as a potential environmental trigger or exacerbating factor in autoimmune disease development and outcomes.
Chemical exposures
Exposure to certain industrial chemicals like silica and solvents have been associated with increased risk of developing autoimmune conditions. The chemicals may cause immune dysregulation or molecular mimicry. Examples:
- Drug-induced lupus erythematosus caused by certain medications.
- Pesticide exposure linked to higher rheumatoid arthritis risk.
Mercury exposure associated with antinuclear antibodies.
Smoking
Cigarette smoking is associated with increased risk of developing certain autoimmune diseases like rheumatoid arthritis and multiple sclerosis, and can trigger flares or worsen symptoms in people who already have autoimmunity. Components of cigarette smoke appear to stimulate inflammatory pathways that can disrupt immune tolerance.
Vitamin D deficiency
Some research suggests that lower vitamin D levels may raise autoimmune risk. Vitamin D is involved in regulating immune cell responses, so deficiency may impair the ability to maintain tolerance and response to infections. More studies are needed to confirm if vitamin D deficiency is a definitive autoimmune trigger.
Leaky gut syndrome
Increased intestinal permeability or “leaky gut” may allow antigens like bacteria, toxins, or undigested food particles to enter the bloodstream and provoke an immune reaction that leads to chronic inflammation and potential autoimmunity. Intestinal hyperpermeability is associated with several autoimmune diseases but more research is required to determine if it is a contributing cause.
Imbalanced gut microbiome
Disruption of the natural balance of intestinal microbes (gut microbiome) has been linked to autoimmune diseases. Animal studies found that transfering gut bacteria from autoimmune-prone mice triggered autoimmunity in healthy mice. Certain bacteria like segmented filamentous bacteria (SFB) produce immune stimulating molecules that may disrupt tolerance. Probiotics or prebiotics may help restore proper microbial balance and reduce autoimmune risk.
Conclusion
The development of autoimmune disease likely involves a complex interplay between genetic vulnerabilities and environmental exposures that trigger the immune system to attack the body’s own tissues. Research continues to uncover clues about which genes may raise susceptibility as well as how factors like infections, gut bacteria, toxins, diet, stress, and other exposures may initiate autoimmunity. Understanding the multifactorial causes can help identify ways to prevent autoimmune disease in those at increased genetic risk by avoiding or modifying environmental exposures. Developing more advanced treatments will also depend on elucidating all the diverse autoimmune pathways so they can be targeted for correction by therapies that reinstate immune tolerance. While the causes of autoimmunity are still not fully understood, the two primary theories of genetic predisposition combined with environmental triggers provide important insights into the potential origins of these complex, chronic illnesses.
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