What Causes Autoimmune Disease?

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An autoimmune disease is best described as a condition, in which the immune system mistakenly attacks healthy cells in the body. Autoimmune disease can affect any part of the body, triggering inflammation, which can lead to redness, heat, pain, and swelling.

The incidence rates of autoimmune disease are increasing worldwide by 4 to 7% every year, with the greatest increases in celiac disease, type 1 diabetes, and myasthenia gravis – a rapid fatigue of the muscles. And according to The National Institutes of Health (NIH), up to 23.5 million Americans currently suffer from one or more autoimmune disease!

What causes autoimmune disease?

Though there is no singular cause of autoimmune disease, there have been multiple variables linked to the onset of this condition, including genetics and environmental triggers. Studies have shown that genetic predisposition accounts for roughly 30% of all autoimmune diseases, but the remaining 70% are the result of environmental factors, like toxic chemicals, diet, infections, and gut dysbiosis. This means that early detection of predictive biomarkers can be used to identify, slow down, and even reverse autoimmune disease.

Toxic Chemicals and Food Triggers

Environmental toxins enter the body by triggering antigen-presenting cells (APCs) which are usually macrophages or dendritic cells. The role of APCs is to sound the alarm to the entire immune system that suspicious particles have entered the system. This process stimulates the release of both inflammatory and anti-inflammatory cytokines into circulation. Anti-inflammatory cytokines will trigger T-regulatory cells to monitor the reaction, while pro-inflammatory cytokines will trigger inflammation and auto-antibody production.

T-regulatory cells have the power to intervene in this process and stop the inflammatory immune reaction by developing immunological tolerance. However, if T-reg cells do not intervene, then naive T cells will continue reacting and eventually develop into TH1, TH17, or TFH cells. These immune cells can trigger autoimmune disease by inducing inflammation, damaging tissues, and producing antibodies. It is the breakdown of immunological tolerance that ultimately leads to an autoimmune response within the body.

Toxic chemicals can also enter the tissue directly and form covalent bonds with healthy cells in the body, making them completely unrecognizable to the immune system. T cells will come into contact with these covalently-bonded cells and stimulate B cells to produce antibodies against the unrecognizable healthy cells. This is how the body begins to attack its own healthy tissues.

Some of the toxic chemicals and foods that can trigger autoimmune disease include: bisphenol A (BPA), mercury, asbestos, mycotoxins, trichloroethylene (TCE), benzoquinones, formaldehyde, ethylene oxide, penicillins, cigarette smoke, nail polish, sodium, gluten, dairy, and glyphosate (1). Though these environmental factors may have different mechanisms of action, they can all increase the risk of autoimmune disease. Take these examples listed below:

  • Nail polish contains halogenated compounds that can bind to mitochondrial proteins, changing their immunogenicity and inducing anti-mitochondrial antibodies (2).
  • Cigarette smoke and alcohol consumption can induce changes in gene expression through the modification of DNA methylation (3).
  • An excess uptake of salt can affect the innate immune system by interfering with macrophage function through TH-17 cells (4).
  • Drinking cow’s milk may induce autoimmunity due to cross-reactivity of its albumin component with islet cell antigen-1 and beta cell surface protein (5).
  • A wheat-based diet induces not only TH1-type cytokine bias in the gut but also increased T-cell reactivity to gluten, with a higher frequency of diabetes (6).

Pathogens Associated with Autoimmune Disease

In addition to toxic chemicals and foods, pathogens can also trigger an autoimmune response within the body. Pathogenic infections can stimulate autoimmune disease in four different ways: molecular mimicry, epitope spreading, dysregulation of immune homeostasis, and the bystander effect.

Molecular mimicry is a process by which an organism can evade detection through molecular camouflage. Certain pathogens can develop epitopes of themselves that look exactly like epitopes of healthy human tissues which allows the pathogen to avoid immune detection and proliferate within the cells.

Epitope spreading is a mechanism much like planting a grenade behind enemy lines. Some pathogens can get into healthy cells and hijack the machinery such that it produces proteins that favor the virus or bacteria. Eventually, these proteins force the once healthy cell to burst and release epitopes throughout the body.

Immune dysregulation occurs when the immune system remains stuck in the inflammatory phase that breeds autoimmune disease. The immune system should shift from the inflammatory phase into an adaptive phase, where it begins to develop oral tolerance, but many times the immune system can get stuck in the inflammatory phase, which acts as a breeding ground for autoimmune disease.

The bystander effect occurs when healthy tissue becomes collateral damage. When a virus or bacteria infects healthy tissue, it causes inflammation in that tissue which calls immune cells like natural killer cells to the scene. These immune cells are designed to attack infected tissue, but they are not selective in the tissue they can damage. When healthy tissue is damaged, it releases tiny compounds that can be antigenic – telling the immune system to continue attacking innocent, healthy tissues.

Pathogenic infections have been associated with a vast number of autoimmune diseases (7-8). This table depicts some of the more common pathogen-associated autoimmune diseases.

Autoimmune Disease Associated pathogen(s)
Rheumatic fever Streptococcus pyogenes
Guillain-Barre syndrome Campylobacter jejuni, Cytomegalovirus, Epstein-Barr virus
Type 1 diabetes mellitus Coxsackie virus B4, Rubella virus, Cytomegalovirus
Lupus erythematosis Epstein-Barr virus
Thyroid autoimmunity Yersinia enterocolitica, Epstein-Barr virus, Parvovirus, Hepatitis C, Coxsackie virus
Rheumatoid arthritis Yersinia enterocolitica, Streptococcus pyogenes, Campylobacter jejuni, Klebsiella pneumoniae, Hepatitis C, Epstein-Barr virus
Lyme disease Borrelia burgdorferi
Multiple sclerosis Chlamydia pneumoniae, Epstein-Barr, Human Herpes virus 6, Hepatitis B
Sjögren’s syndrome Epstein-Barr virus, Cytomegalovirus, Hepatitis B, Hepatitis C, Coxsackie virus B4, Human T-cell leukemia virus
Scleroderma Cytomegalovirus
Myasthenia gravis Herpes simplex virus, Hepatitis C
Primary biliary cirrhosis Escherichia coli
Reiter’s syndrome Chlamydia trachomatis, Shigella species
Allergic encephalitis Measles virus
Myocarditis Coxsackie virus B3, Cytomegalovirus, Chlamydia
HTLV-associated myelopathy Human T-cell leukemia virus

Gut Dysbiosis

Low microbial diversity in the gut is also associated with increased risk for autoimmune disease and increased incidence of infection (9). One round of broad-spectrum antibiotics, for example, can decimate the gut microbiome, decreasing the microbial diversity for up to two years after the medications have left the system.

Fortunately, beneficial bacteria that reside in the gut, like Bacterioides fragilis, Faecalibacterium prausnitzii, Akkermansia muciniphila, Bacillus spores, and non-infectious Clostridia spp, can all help protect against autoimmune disease through the up-regulation of the T-reg system, suppression of TH-17, restoration of the intestinal mucus layer, and the reduction of systemic inflammation (10). In this way, reconditioning the gut microbiome can help prevent and correct autoimmune responses within the body.

Summary

In summary, autoimmune disease can be triggered by toxic chemicals, dietary components, pathogenic infections, and gut dysbiosis.

Environmental health solutions:
  • Dramatically reduce sodium intake
  • Grow your own food when possible to minimize glyphosate exposure
  • Use natural household cleaners when possible
  • Avoid skincare or cosmetics that aren’t safe for human consumption
  • Avoid gluten and crops that use glyphosate for dessication (corn, potatoes, barley, oats, etc)
Gut health solutions:
  • Consume a diversity of fruits and vegetables to improve microbial diversity
  • Take Bacillus spores to help repair leaky gut and improve microbial diversity
  • Avoid prolonged antimicrobial use when possible
  • Keep fat intake below 30% of daily caloric intake to up-regulate the T-reg system
  • Fast 14-16 hours daily (intermittent fasting)
  • Consume prebiotic fibers like xylooligosaccharies (XOS), fructooligosaccharides (FOS), and galactoligosaccharides (GOS) that feed only beneficial bacteria to improve microbial diversity
  • Supplement with IgG powder, L-glutamine, or a combination of L-proline, L-serine, L-threonine and L-cysteine to repair leaky gut

References

  1. Vojdani A. A Potential Link between Environmental Triggers and Autoimmunity. Autoimmune Diseases. 2014;2014: Article ID 437231.
  2. Rieger R, Gershwin ME. The X and why of xenobiotics in primary biliary cirrhosis. Journal of Autoimmunity. 2007;28(2):76-84.
  3. Bigazzi PE. Autoimmunity caused by xenobiotics. Toxicology. 1997;119(1):1-21.
  4. Machnik A, et al. Macrophages regulate salt-dependent volume and blood pressure by a vascular endothelial growth factor-C–dependent buffering mechanism. Nature Medicine. 2009;15:545-552.
  5. Cavallo MG, et al. Cell-mediated immune response to β casein in recent-onset insulin-dependent diabetes: implications for disease pathogenesis. Lancet. 1996;348(9032):926-928.
  6. MacFarlane AJ, et al. A Type 1 Diabetes-related Protein from Wheat (Triticum aestivum) cDNA Clone of a Wheat Storage Globulin, Glb1, Linked to Islet Damage. J Bio Chem. 2003;278:54-63.
  7. Fairweather D, Rose, NR. Women and Autoimmune Diseases. Emerg Infect Dis. 2004 Nov; 10(11): 2005–2011.
  8. Ercolini AM, Miller SD. The role of infections in autoimmune disease. Clin Exp Immunol. 2009;155(1):1-15.
  9. Ozdemir O, Goksu-Erol AY. Probiotics for Autoimmune Diseases: Is There a Benefit? Contemporary Pediatrics. 2012:153-180.
  10. Campbell AW. The Gut, Intestinal Permeability, and Autoimmunity. Alt Ther Health Med. 2015;21(1):6-7.155(1): 1–15.

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