Possible Environmental Triggers Associated with Autoimmune Diseases

Adapted from a presentation given at the SLE Workshop at Hospital for Special Surgery

George Piligian, MD, MPH
Assistant Clinical Professor
Selikoff Center for Occupational & Environmental Medicine
Department of Preventive Medicine
Mount Sinai Medical Center

Helen Lee, MD, MPH
Assistant Clinical Professor
Selikoff Center for Occupational & Environmental Medicine
Department of Preventive Medicine
Mount Sinai Medical Center


Introduction

Dr. Piligian began his presentation with three points of clarification. He first explained that his primary focus as a physician is treating patients who have experienced illness or injury from the nature of their occupation or their environment. He and his colleagues at Mount Sinai examine, treat, and refer these patients and try to understand causative links between exposures and health outcomes so as to treat the disease or injury more effectively. Additionally, they treat patients whose prior conditions have been exacerbated as part of their work or as a result of exposures in their environment in order to prevent disease progression.

Secondly, Dr. Piligian cautioned the group to be smart consumers of information. Highlighting the word “Possible” in the presentation title, Dr. Piligian stressed that much of the research the medical and scientific community has generated about environmental triggers of autoimmunity isn’t proven beyond a reasonable doubt. Autoimmunity is the failure of an organism to recognize its own bodily make-up, so that it begins to attack itself.

Finally, Dr. Piligian made clear that hypothesized agents that may be possible triggers of the autoimmune response are not necessarily causes of autoimmune illnesses. Causation is very complex and involves the interaction in individuals between their genes, how their genes are modified, how their body reacts to the environment, and other factors we are probably not aware of yet.

With that disclaimer, Dr. Piligian said that it is important for individuals to be aware of the available research on preventative measures but to apply these measures in the appropriate context of living and enjoying life. Context is important because recommendations made out of context could cause more harm than good in an individual’s life.

Mechanisms of Environmental Triggers of the Autoimmune Response

Dr. Piligian began by explaining two of the several theories that explain how environmental factors impact autoimmunity: inflammation and epigenetic control of genes.

Inflammation

When there is inflammation due to a foreign invader within the body, the parts of the cells of the body that are injured are not in their normal state. The injured cells attract other cells that inspect the area and may interact, for instance, to clean up debris from the injury. In the region of injury, parts of the body’s cells that are recognized as foreign by the inspector cells are labeled as “antigens” because they can stimulate production of corresponding “antibodies” in the body. Immune system cells that serve as “inspector cells,” for example, can remember or imprint an antigen molecule. From this imprint, antibodies can be created that bind to the specific antigen. The antibody may attack the antigen substance or not, depending on a variety of factors.

This process is called immune reactivity, and if the body is reacting to cells in the body that are not invaders from outside the body but are the body’s own cells, then it is called “autoimmune” reactivity. If the body is reacting to a foreign invader, that is necessary.  But if it is also reacting against itself, then it is triggering or exacerbating the autoimmune process.

Epigenetic Control of Genes

The second theory Dr. Piligian explained is called epigenetic control of genes. This is a process where the expression of a gene is altered without changing the DNA sequence. DNA is the original instruction plan or “blueprint” for our body, and all of the cells express themselves according to these given instructions.

In epigenetic control, exposure to harmful substances that can enter the cells of our body can change the expression of a gene (what is produced by the DNA), without actually altering the original DNA instructions. Typically, this process either results in expressing something that should not be expressed or repressing something that should be expressed from the DNA.

Environmental Exposures that May Be Associated with Autoimmunity

Dr. Piligian then spoke about three environmental exposures that can impact autoimmunity. The three factors mentioned were 1) infections, 2) substances found in one’s occupational environment, and 3) substances found in the environment in general.

Infections

Discussing infections, Dr. Piligian reminded us that these occur when our body is exposed to a foreign living substance. There are different types of infections caused by different foreign substances. An infection can be produced, for instance, by bacteria, viruses, or parasites.

Bacterial and viral infections are thought to impact the autoimmune response by a process called molecular mimicry. This is when a foreign substance is shaped very similar to a naturally occurring substance in the body, essentially blending into the body like camouflage. Parasitic infections can induce inflammation in this manner, which is thought to impact the autoimmune response.

Occupational Exposures

Much of our knowledge about environmental dangers comes from occupational cohort studies. A cohort is a group of individuals who have a shared experience. In occupational or environmental health research, the study of workers who have had similar exposures, and are afflicted with similar conditions, has helped to identify possible associations of environmental exposures and certain diseases.

Nevertheless, researchers Molina and Shoenfeld have written, “The majority of the autoimmune connective tissue diseases have no known etiological agents. However, certain drugs, occupational and environmental actors have undoubtedly been shown to either exacerbate a known autoimmune disease or to trigger the onset of a syndrome that closely resembles one of the established diseases.”

Systemic sclerosis, for example, which is an autoimmune disease, has been associated with occupational exposure to silica dust (a dust that arises from crystalline quartz and has been shown to cause breathing problems in workers in mining, stone cutting, quarrying, blasting, road and building construction, and farming). Solvents, which are derived from crude oil, such as benzene, trichloroethylene (used to clean metals in industrial settings), or perchloroethylene (a colorless liquid used in dry cleaning) also can induce systemic sclerosis.

General Environmental Exposures

Dr. Piligian reported that a disease similar to scleroderma has been associated with silicone implants, with the accompanying severe pain and chronic fatigue. Lupus antibodies (anti-Sm& anti-RNP) have been detected in patients with silicone implants, and these antibodies disappeared once the implant was removed. Hydrazines (colorless and flammable liquid, with an ammonia like scent) occurs in tobacco, and is commercially used in making plastics, anti-corrosives, rubber products, herbicides, photographic supplies, preservatives, textiles, and dyes, have been associated with drug-induced lupus in some studies. Certain metals, such as mercury, have also been identified as possible triggers of autoimmune processes in the body. Epidemiologic data is still accumulating on these associations and it’s possible they will be disproved with more evidence.

Genetics and hormones may also interact to create autoimmune processes, such as the hormone estrogen. While estrogen’s link to certain diseases is not fully understood, we do know that females, where the estrogen hormone dominates, have experienced more of the autoimmune diseases. Men who have an extra female chromosome, resulting in more estrogen production, also experience an increased risk of autoimmune illnesses in some studies. The association of autoimmune diseases and estrogen is inconsistent in the epidemiologic literature; however, it is a predominant hypothesis for explaining the disparity in incidence among males and females.

Techniques for some Possible Preventive Measures

Dr. Piligian then posed an important question: “What do we do with this information? How can we make this useful in our everyday lives?”

Again, Dr. Piligian stressed that it is very important to apply preventive measures within reason. One way he mentioned to gauge if the preventive measure is reasonable is if you could apply the advice to yourself before advising it to patients. The following tips are not specific to autoimmune illness only, but are of a general nature and would be of benefit to most people. For those living with an autoimmune disease, applying these principles may help slow the disease’s progression and improve overall quality of life.

The first part of protecting one’s body from triggers in the environment is also being protective of what you feed your body. Good nutrition is important - specifically anti-inflammatory foods, which are found in nature. Overly processed foods may add unhealthy ingredients or strip away nutrients that are naturally present. Ensuring that you get adequate rest and sleep is critical. During sleep and rest, the body takes time to repair itself. This process is vital to the immune system and helps in buffering us from illness. Engaging in appropriate exercise is important as well.

Perhaps the most important tip that Dr. Piligian dispensed that day is to “relax, forgive, and enjoy.” He pointed out that the absence of these three actions can also have physical consequences such as an increase in the stress hormone cortisol. Too much cortisol in our system can cause ill health. Conversely, when we relax, forgive, and enjoy, endorphins, which are natural feel good chemicals, are released into our body and have a positive impact on our short- and long-term health.

Acknowledging that the field of research on environmental triggers of autoimmunity is in its infancy, Dr. Piligian left the SLE Workshop with a request.

He said the way science and medicine advance can be very slow and arduous, because we need replication of results in order to have confidence in our understanding of the causes of disease. This costs a lot of money, and money for studies is not easy to find. He urged us to advocate as a group for more research dollars for this topic.

With more research comes the possibility of more discovery and potentially better ways to protect ourselves from harmful substances that could trigger autoimmune disease.

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Summary by Lysa Silverstein, Social Work Intern and SLE Coordinator

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