Assessing and treating autoimmunity
It’s never simple when dealing with the whole system, said Robert Rountree, MD, and Richard Mayfield, DC, CCN, DACBN, at the 2018 Institute for Functional Medicine (IFM) Annual International Conference in Hollywood, Florida.
A systems-model approach is the key when dealing with autoimmune disease, said Rountree, who uses his model, Functional Toxicology, to work on all aspects of autoimmunity with patients:
Toxicants → Molecular Triggers (cell stressors)
Antecedents (Genomics, lifestyle)
The human exposome represents the combined exposures from all sources that reach the internal chemical environment. This can be broken down in to the internal chemical environment—xenobiotics, inflammation, preexisting disease, lipid peroxidation, oxidative stress, and gut flora— exposome – reactive electrophiles, metals, endocrine disruptors, immune modulators, and receptor-binding proteins—and the external environment—radiation, stress, lifestyle, infections, drugs, diet, and pollution. Signatures and biomarkers can detect these agents in blood or serum.
Commonly encountered xenobiotics included:
- Petrochemical fuels and solvents
- Pigments, paints, dyes, and perfumes
- Preservatives and flame retardants
Without a doubt, environmental factors contribute to autoimmune disease, and a growing body of research supports this notion. Heavy metals have been linked to autoimmune glomerulonephritis. Dietary factors are linked to type 1 diabetes. Ionizing radiation is linked to systemic lupus. Stress has been linked to rheumatoid arthritis.
A 2004 study in the journal Environmental Health Perspectives found a “dose-related early appearance of elevated anti-double-strand DNA titers that corresponded with subsequent development of glomerulonephritis.” In 2002, a meta-analysis of 13 studies in the journal Epidemiology found several biological models that could explain how organic solvents affect individual susceptibility to multiple sclerosis, including possible damage to the blood-brain barrier.
Potential mechanisms for xenobiotics and autoimmunity, according to Rountree and Mayfield, include modifications of self-antigens, activation of innate/adaptive immunity via Toll-like receptors, adjuvant effects and inflammatory responses, B cell activation and checkpoint dysfunctions, upregulation of T-helper 17 (TH17) cells, and suppression of T-regulatory cells.
The aryl hydrocarbon receptor (AhR) links TH17 cell-mediated autoimmunity to environmental toxins. The AhR is best known for mediating the toxicity of dioxin and other organochlorine compounds, like PCBs. Environmental factors are believed to contribute to increased prevalence of autoimmune diseases, many of which are due to the activity of IL-17 producing T cells. AhR activation during induction of experimental autoimmune encephalomyelitis causes accelerated onset and increased pathology in wild-type mice, but not AhR-deficient mice. AhR ligands may therefore represent co-factors in the development of autoimmune diseases, said Rountree.
“Many xenobiotic triggers of autoimmune diseases have been found to act as xenoestrogens,” said Rountree. “The potential mechanism for this may be endocrine disruption.”
Endocrine disruptors are natural or synthetic compounds that, through environmental or inappropriate developmental exposures, alter the hormonal and homeostatic systems that enable the organism to communicate with and respond to its environment. Common xenoestrogens include organochloride pesticides, dioxins, parabens, steroids given to livestock, and mycotoxins.
However, the best example of an endocrine disruptor is diethylstilbestrol (DES). In the 1950s, DES was administered during pregnancy to prevent premature birth. It was later promoted for all pregnant women as a supportive therapy. Up to 10 million Americans received DES during pregnancy or were exposed to it in utero. A 1988 study published in Fertility and Sterility found an increased occurrence of autoimmune disease among women exposed to DES in utero.
It’s nuances like these that make looking at the whole picture so important for autoimmune disease patients. Toxins from the environment, from the diet, and genetic pre-dispositions must all be considered when addressing autoimmunity in patients.
“It’s not magic,” said Rountree. “You do need to approach the entire system. It’s all part of the mix. We have to consider that when working with patients.”
Editor’s note: This article is part of Integrative Practitioner’s live coverage of the Institute of Functional Medicine’s 2018 Annual International Conference. For a full list of coverage, click here.