Genetics, immune dysfunction and chronic illness...
I've discussed in previous blog posts the role of the immune system and effects of an antigen that in some can contribute to immune dysfunction. We find this scenario in PANS, autoimmune encephalopathy and neurological Lyme diseases.
Genetics can also contribute to this dysfunction. In addition to infectious agents or antigens, the immune system also must clear toxins from the body. Toxins are bi-products of cellular processes that occur daily, die-off from dead bacteria, parasites and viruses or environmental exposures to chemicals, heavy metals and molds.
Toxins also trigger inflammatory responses much like infectious agents. The immune system likes the nice balance of a bell curve. It prefers to be in the middle! If it struggles to clear an infection ,the burden may be too great to effectively deal with environmental exposures and other debris further compounding the scenario.
I'm often asked why some individuals exposed to illnesses are unaffected while others prove to suffer devastating symptoms sometimes long-term in nature.
Many, MANY factors can attribute to some healing relatively unscathed while others suffer tremendously. This is where I believe genetics play a role, specifically MTHFR, COMT and CBS polymorphisms.
Poly-who? What's a polymorphism? Unlike genetic mutations that occur as a result of a change in genetic material via a coding errors during replication or exposure to a mutagenic substance, Polymorphisms are a change of the DNA sequencing usually as an adaptive trait to the individuals environment over time. It's typically positive in its effects and is common in the general population. Typically polymorphisms do not promote any significant health risks but we are finding trends among certain genetic sequencing in chronic illness that lead to a clear set of symptoms. Polymorphisms much like genetic mutations can be inherited.
Back to MTHFR, COMT and CBS. These genes function to remove toxins, inflammatory markers and support neurotransmitter function directly and indirectly thru enzymatic conversions of substances.
What do they do?
Cystathione Beta Synthase or CBS for short is the gatekeeper of homocysteine and the pathway that produces ammonia. With a CBS polymorphism triggers increased enzymatic activity and breaks down homocysteine too quickly allowing for ammonia buildup. Ammonia is toxic to the body specifically the neurological system. Also by virtue of this increased activity, sulfur groups known to play a roll in the intricate methylation cycle are quickly released in the body as sulfites, also toxic to the body.
Clinically those with CBS mutations have an intolerance to sulfur derivatives like the antibiotic Bactrim or with ingestion of high sulfa foods like leeks, broccoli, curcumin, sprouts, onion, garlic etc. Also higher protein diets can trigger ammonia build up given the higher levels of B6 which can further activate the ammonia buildup.
Elevated ammonia or sulfite levels can lead to a barrage of symptoms. Lethargy, combativeness, irritability, mood swings, low temperature, poor coordination, seizure, headache, nausea, vomiting diarrhea are all common symptoms.
Catecholomethyltranserase or COMT is responsible for the breakdown of catecholamine neurotransmitters such as epinephrine, norepinephrine and dopamine. COMT's main function is to regulate these neurotransmitters. Normal COMT function allows a person to quickly reverse feelings of anxiety or depression. Those with these polymorphisms may suffer from clinical depression or other mood disorders. COMT variants are also responsible for pain receptors. Individuals with multiple COMT copies may suffer a lower threshold for pain.
Another important responsibility of COMT is to assist with the breakdown of estrogen in the body. Those with estrogen dominance will note a slower COMT function further compounding the associated mood disorders of imbalanced dopamine levels.
Clinically, those afflicted with a chronic illness and multiple COMT mutations have difficulty managing pain and mood in stressful environments.
Methylene tetrahydrofolate reductase or MTHFR is one of the many enzymatic processes responsible for methylation in the body. Methylation is a biochemical process that involves adding a methyl chemical group to a vitamin or neurotransmitter that will allow for specific interactions with the cell. Methylation is important for the cellular delivery of many nutrients specifically folate.
Folate is one of the components responsible for the breakdown of homocysteine once the immune system no longer has a need. Lingering elevated homocysteine levels can contribute to varied ailments known to occur as a result of inflammation . If the process responsible for converting folate isn't working properly, your vitamin B12 levels may also suffer as B12 is dependent upon folate to activate within the body. B12 also plays a roll in the breakdown of homocysteine.
Folate and B12 drive many processes in the body. The cardiovascular and neurological systems rely upon them heavily to maintain equilibrium and health. Cellular absorption of B12 is responsible for stimulating the secretion of serotonin for mood support as well as contributing to detoxification of debris from cells. Folate deficiencies as a result of possessing MTHFR mutations have shown to contribute to neuropsychological disorders increased risk of cardiovascular disease, accelerated aging, autoimmune diseases, poor detoxification pathways and many other ailments. Taking methylated forms of B12 and folate along with healthy diet, detox support and addressing any underlying illnesses albeit acute or chronic in nature can help to prevent further issues.
Carrying one or more of these polymorphisms is not a guarantee that you'll suffer any health consequences but rather create more vulnerability when faced with chronic infections. Have you noticed a trend? It's about inflammation and detoxification pathways!
Many individuals suffering from Neurological Lyme and other tick-borne illnesses many times carry one or more of these genetic polymorphisms. We find that these individuals have higher levels of pain, incredibly difficult detoxification pathways and significant neurological symptoms compared with those that do not carry the genes. Most diagnosed with PANS/PANDAS or autoimmune encephalopathy carry these polymorphisms as well.
Remember when dealing with immune dysfunction and chronic illness, there is never a singular event as the cause!