Molecular Mimicry as a Mechanism of Autoimmune Disease

Autoimmune conditions affect around 4% of the world's population. And the rate is rising by about 3 to 7% per year. This represents a significant burden of disease and disability for humanity and a concerning trend. But why would the body use the immune system to attack its own critical cells? 

One of the major reasons is molecular mimicry, where two structurally similar compounds can fit into the same receptors due to their similar shapes and interfere with the physiological process. For example, when the body is fighting an infection, the immune system will detect the infected cells based on their shape. But if a human cell of a similar shape fits into the receptor instead, the body may attack the human cells along with the virus, and an autoimmune condition could arise. 

This article will discuss molecular mimicry, its role in autoimmune conditions, how functional medicine can help determine the causes of autoimmunity, and how to approach it with a holistic perspective.

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What is Molecular Mimicry?

In biological systems, certain molecules fit together like a lock and key. The metaphorical door can be opened when the "key" molecule fits into the "lock" part of other molecules. In other words, the molecule's shape determines whether it can have an effect on other cells.

In the same way, structurally similar parts of completely different structures can be close enough in form that one can substitute for the other, creating the same reactions. Depending on what is involved, this can be helpful or not helpful. 

In the case of molecular mimicry contributing to autoimmunity, it occurs when protein structures from foreign sources and self are similar enough to fit into the same lock and unlock the same door. In this case, unlocking the door triggers an immune response against the one who opened it. This is useful if the target is a virus or a bacteria but potentially harmful if it is a protein associated with one's own cells. 

Molecular mimicry is one of the ways infections or chemical exposures may contribute to autoimmunity. 

What Causes Molecular Mimicry?

If molecular mimicry happened every time two structures were similar, it would be far more common than what we see. So other factors must affect whether or not it happens in a given situation. Below are some potential contributors to autoimmune conditions associated with molecular mimicry. 

Gut Health

Gluten is a potential contributor to autoimmunity due to molecular mimicry. Gluten can affect the overall gut health of susceptible individuals, including its influence on the microbiome. 

Nutrient Deficiencies

Certain nutritional deficiencies have been shown to contribute to the onset of autoimmune conditions. Western diets, specifically, can affect the immune system because of the imbalance of essential nutrients. 

Inflammation

Chronic inflammation is a known contributor to autoimmune conditions. Molecular mimicry may induce inflammation, which then could contribute to autoimmunity. 

Hormones

Thyroid autoimmune conditions, namely Hashimoto's, occur when the immune system attacks the thyroid. Gluten is a known contributor due to the molecular mimicry between gluten and thyroid hormones. Stress hormones, in excess chronically, can also increase the risk of autoimmune conditions.   

What is Molecular Mimicry's Role in Autoimmune Disease?

Molecular mimicry can influence the immune system to mount a response against the self. This may contribute to the development of an autoimmune condition. 

One example is the potential interaction between gluten and the thyroid gland. Because there are parts of gluten and thyroid cells that are similar enough, gluten can influence the immune system to attack the thyroid under the right circumstances. Once this has occurred, future gluten exposure can also increase the attack against the thyroid (increasing anti-thyroid antibodies).

It has also been found that similarities in structure between certain bacterial protein fragments and fragments of gluten proteins may be key in contributing to gluten disorders, including Celiac disease.

It turns out that the brain also can experience molecular mimicry-related autoimmunity as a result of cross-reactivity with gluten proteins. This is hypothesized to be a possible contributing factor to neurodegenerative disorders. 

Another example of molecular mimicry contributing to an autoimmune disease is the group A strep infections, which can be associated with acute rheumatic fever, rheumatic heart disease, and other autoimmune issues. 

Functional Medicine Labs to Test for Patients with Molecular Mimicry and Autoimmune Disease

Functional medicine labs can help practitioners understand whether a potential molecular mimicry situation is contributing to an autoimmune condition. Below are some of the most commonly run labs and panels:

Gut Health Testing

Given the apparent number of autoimmune conditions that may be related to gluten and the known connections with gut health, GI health would be a very appropriate place to start with functional testing for autoimmune disease. Assessing gluten reactivity can give insight into whether gluten may be a contributing factor to illness and should be removed from the diet. 

A food allergy panel can identify other foods that may be contributing to immune activation and inflammation, both risk factors for molecular mimicry. 

Microbial balance and intestinal barrier integrity are very important factors for immune health. The GI-MAP + Zonulin test can show if dysbiosis or leaky gut are factors that may be contributing to an autoimmune condition. 

Lastly, the microbiome is crucial for the immune system and regulating systemic inflammation levels. The BiomeFx test can give a snapshot of the current balance of the microbiome and insights into possible approaches to rebalance.

Nutritional Testing

Evaluating nutritional status is also important, especially if the diet is inadequate or there is a suspected gut issue potentially impairing the absorption of nutrients. Micronutrients are required for healthy cells, and deficiencies in these micronutrients can contribute to autoimmune conditions. The cellular nutrition assay shows micronutrient status as well as personalized recommendations for antioxidants, which is relevant for autoimmune issues. 

Inflammatory Testing

Inflammation plays a key role in the onset of autoimmune diseases. Markers of inflammation can be tested before treatment to assess the starting point of inflammation in the body and after treatment to monitor the progress. 

Hormonal Testing

Thyroid autoimmunity (Hashimoto's) is the most common cause of hypothyroidism in the USA. Therefore, assessing the thyroid via a Thyroid Panel is critical when evaluating overall autoimmunity. This is especially important if hypothyroid symptoms are present or if gluten is a suspected trigger in an individual's situation. 

Dysregulation in the HPA axis, also known as the stress response, can predispose someone to an autoimmune condition. Assessing the stress hormones via an adrenal panel can help distinguish whether this is a factor for an individual.

How to Support Your Autoimmune Disease Patients

From a root cause perspective, there are a few goals in managing autoimmune disease. One of the major places we can affect change is in the levels of inflammation present. One of the other things is to shift stress levels and stress response. Nutrition, herbs, and yoga/meditation can all be useful for these goals. 

Nutrition 

The main goal of nutrition is to limit additional inflammatory triggers while optimizing foods that naturally support a healthy inflammatory response in various ways. Balancing overall nutritional needs is also important. A Mediterranean diet, including abundant colorful fruits and vegetables, phytonutrients, vitamins, minerals, fiber, omega-3 fatty acids, and monounsaturated fatty acids, has been shown to help support a healthy inflammatory response and improve the composition of the gut microbiome. Intermittent fasting is also a dietary habit shown to support a healthy inflammatory response. 

It is also important to avoid foods that appear on a food allergy or food sensitivity test, as these are immune triggers. In existing autoimmune conditions, gluten would also be worth avoiding completely due to the higher risk for molecular mimicry and the generally unhelpful effects on gut barrier health. 

Sugar may also contribute to triggering autoimmune conditions and would thus be better avoided, especially if an autoimmune condition already exists. 

Complementary and Alternative Medicine

In alignment with reducing immune activation and low-grade inflammation, there is evidence as to the usefulness of some alternative therapies, including supplements.

In addition to a dietary focus on consuming more natural sources of omega-3 fatty acids, it may often be helpful to consider doses that are more accessible through supplementation, such as fish oil.

Curcumin is a powerful herb for supporting a healthy inflammatory response. It has also been recently studied specifically in relation to autoimmune conditions and is generally found to have a beneficial effect with a low risk of adverse effects. 

Vitamin D may play a role in maintaining a healthy gut barrier and a healthy microbiome, which support the body's natural defenses against autoimmune processes and excess inflammation.

Probiotics help restore a health-promoting gut ecosystem, which is generally favorable for outcomes with autoimmunity.  

In addition, due to the connection between stress and immune function, some other potentially supportive modalities may be beneficial. Modalities such as massage and acupuncture can be helpful in rheumatic autoimmune diseases. These therapies assist in lymphatic circulation and drainage, which are often compromised in individuals with autoimmune conditions. 

Yoga has been shown to be beneficial for balancing the stress response and for symptom management in those experiencing various autoimmune conditions. 

Summary

Molecular mimicry is a significant process through which autoimmune conditions may be triggered. It occurs when foreign molecules are shaped similarly to human cells, and cross-reactivity happens. This can be confusing to the immune system, and eventually, this may influence the immune system to believe that certain human cells should be attacked. 

Functional medicine labs can help assess whether molecular mimicry could be occurring. Then, utilizing the information from these labs can help create individualized approaches to support the management of autoimmunity.