Breakthrough Research Finds CFS is An Immune Condition
Australian scientists have linked chronic fatigue syndrome (CFS) to a genetic defect in immune cell receptors putting to rest once and for all the pathology of this much-maligned condition.
The research undertaken by the National Centre for Neuroimmunology and Emerging Diseases (Griffiths University) found that an inherited genetic defect means that cells do not work optimally.
These findings have potentially wider implications as many of the patients studied also had fibromyalgia and postural orthostatic tachycardia syndrome.
Mast-cell precursors have also been found in the blood of the patients studied.
Whilst CFS patients might well fall under the spectrum of mast-cell activation, the Griffiths University research, by identifying the mechanism of action, provides a much more precise diagnosis.
CFS Genes Studied
Griffiths University is studying a pattern of single nucleotide polymorphisms (SNPs) in the TRP and acetylcholine receptors (AChM3R). If you have done a 23andMe test, you can use livewello.com, to extract the following indicative data.
Current CFS Research Findings
The receptors being studied by Griffiths University are not well researched. They are however known to act as part of a primitive “threat” sensing system.
Acetylcholine coordinates the brain’s response to environmental stimuli, either dialing up or dialing down, its response based on the level of perceived threat. It is also highly susceptible to acute psychological stress.
TRPA1 channels, for example, are cellular “threat” sensors that detect cellular oxidative stress and a range of stimuli both within and outside the cell.
It senses temperature, touch, pain, smoke, chemicals, solvents, mold, cold pain, and all manner of stimuli. It also appears to sense some medications.
Once TRPA1 channels are stimulated, TRPM3 moves calcium into the natural killer (NK) cell in order for it to work.
Griffiths University found that the TRPM3 receptors on natural killer (NK) cells are impaired with CFS. They fail to move calcium into the NK cell, which results in decreased cell function and specifically decreased cytotoxic killing ability.
In a presentation, by the researchers themselves, that I attended at Griffiths University, they clarified that although this mechanism was not just impaired in the natural killer cell but all cells.
Natural Killer Cells
Natural killer (NK) cells are cells belong to the innate immune system.
This is the part of the immune system that does not require previous exposure to certain types of threats in order to work. NK cells have a primitive ability to recognize stressed cells regardless of previous exposure.
NK cells can be divided into two categories and differentiated by the types of markers on them.
Cytokines – The first type is mainly capable of secreting cytokines, that act as mediators between different cells of the body, mainly cells of the immune system. They disrupt and contain the virus from spreading and facilitate the entry of the NK cells into the affected cell. This process is not necessarily impaired in CFS patients.
Cytotoxic Activity – The second type has cytotoxic activity, meaning that it can kill abnormal body cells, such as virus-infected, or cancerous cells. Griffiths University found that CFS patients have decreased cytotoxic activity of the NK cells.
Preferential Calcium Channel
Both TRPA1 and TRPM3 are parts of the preferential calcium channel which moves calcium into the cell to mount the NK cell’s defense.
Calcium is found in virtually every cell in the body and acts as a biological messenger responsible for carrying signals, through calcium channels, to target activities within cells. NK cells are no exception and require calcium to regulate their cellular functions.
TRPM3, however, has a secondary pathway distinct from the central pore that can be specifically activated by the combined application of Pregnenolone Sulfate and/or Clotrimazole, a drug used to treat yeast infections. Simplistically, this is a backup system, that can help move calcium into the channel when the primary pore is faulty.
What Does This Mean For CFS Patients?
The impact of altering a gene is not yet known. This is what Griffiths University are diligently working on together with the research into other SNPs that might affect overall function.
Whilst Griffith University believes it has found the primary mechanism of action for CFS there is much that needs to still be done to have a comprehensive solution. This includes screening methods.
As of December 2017, Griffith’s University is evaluating the use of Nifedipine (Brand Name Adalat) which is a blood pressure medicine which stimulates calcium rectors helping calcium to enter the cell. This is currently being studied in petrie dishes.
If you are in Australia and have CFS then I would encourage you to consult with Professor Pete Smith.
A Functional Approach
The CFS process is triggered by an “activation.” From a functional perspective, the key question is therefore what is the TRP gene sensing?
Personally, investigation of these, and resolving them, has been highly significant in my own journey with CFS. I still have CFS, and I still get triggered, but my symptoms have improved substantially.
Improve NK Cell Activity
Improvement of NK cell activity may also help including:
Exercise – gradually increased to no more than capacity.
Melatonin: particularly liposomal melatonin which I find particularly helpful with a flare-up.
Digestacure: which I am currently experimenting with.
Calcium and Magnesium
TRPM3 functions as a non-selective calcium channel. It is inhibited by intracellular magnesium – potentially leading to the “work around” secondary TRPM3 channel being activated.
Intracellular levels can be estimated with a hair mineral analysis or Spectra-cell Micronutrient Test.
Personally, liposomal magnesium, IV magnesium, and magnesium sulfate baths have been exceptionally helpful in relieving my own CFS symptoms. Magenesium can also be poorly absorbed due to parasites or other micronutrient deficiencies.
Improvement of the calcium channel function, through reducing exposure to electromagnetic fields, can also be helpful to many CFS sufferers.
Pregnenolone sulfate also activates the secondary TRPM3 channel.
Pregnenolone is synthesized from cholesterol and b vitamins and is considered to be the master hormone of all steroid hormones. Dietary deficiencies or digestive issues can easily compromise pregnenolone levels. When deficient pregnenolone can be supplemented.
However, pregnenolone alone is not sufficient. It needs to be converted to pregnenolone sulfate to activates the secondary TRPM3 channel.
Sulfation is a process that is part of phase II liver detoxification. It can become compromised with inflammation, sulfur deficiency, or glucocorticoid use. Addressing sulphation can, therefore, be helpful to restoring pregnenolone sulfate levels.
Acetylcholine status can be evaluated with the choline marker on a Spectracell Micronutrient Test.
To increase acetylcholine, substances that provide acetylcholine precursors, prevent the breakdown of acetylcholine, or a combination of both can be used. Examples of these combination products are Brain Memory by Douglas Labs, and Acetyl-CH by Apex Energetics.
As acetylcholine is susceptible to acute psychological stress, reduction of psychological stress can be important. Personally, I have used a combination of EFT, mindset, and walking away from stressful situations, with significant benefits.
The Gupta Programme, the Dynamic Neural Retraining System, and The Lightning Process all claim to help CFS by rebalancing the threat system. I have not tried any of these systems, preferring the use of EFT, but know many people who have benefited from these programs.
Methylation is involved in immune cells and natural killer cells. It is also required in the pathway for acetylcholine biosynthesis.
Whether a person is genetically compromised, has impaired digestion and absorption of nutrients, or has a restricted diet devoid of key methylation nutrients, methylation can alter the way cells function.
Whilst this has not been one of my many CFS challenges I have seen simple methylation support make a profound difference in others.
My over-riding approach has been to remove the threats to my body (particularly mold, medications, stress, and dental issues), to create the optimal environment for healing (through lifestyle changes and targeted supplementation), and to support my immune system to calm down.
To a large extent, this has worked. I will always be vulnerable to CFS, and still, have flare-ups, but the symptoms have gradually fallen away.
The articles cited in this article were read by an Associate Professor Of Immunology and summarized for me to ensure that the information above was technically correct.
Marshall-Gradisnik S, Smith P, Nilius B, Staines DR: Examination of Single Nucleotide Polymorphisms in Acetylcholine Receptors in Chronic Fatigue Syndrome Patients. Immunology and Immunogenetics Insights 2015, 7:7-20.
Marshall-Gradisnik SM, Smith P, Brenu EW, Nilius B, Ramos SB, Staines DR: Examination of Single Nucleotide Polymorphisms (SNPs) in Transient Receptor Potential (TRP) Ion Channels in Chronic Fatigue Syndrome Patients.Immunology and Immunogenetics Insights 2015, 7:1-6.
Nguyen T, Johnston S, Chacko A, Gibson D, Cepon J, Smith P, Staines D, Marshall-Gradisnik S: Novel characterization of mast cell phenotypes from peripheral blood mononuclear cells in chronic fatigue syndrome/myalgic encephalomyelitis patients. Asian Pacific journal of allergy and immunology 2016.
Huth TK, Brenu EW, Staines DR, Marshall-Gradisnik SM: Killer Cell Immunoglobulin-like Receptor Genotype and Haplotype Investigation of Natural Killer Cells from an Australian Population of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients. Gene Regulation and Systems Biology 2016, 10 :43-49.
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