It might be a cause of a certain subset in ME/CFS patients.
I was reading through your blog and I must admit, it is one of the most detailed symptomatic blogs on ME that I have read including symptoms usually not listed with ME such as tooth decay, neurological -memory, speaking, writing, winkling of the skin, vision etc. Many ME patients do have these additional symptoms. Most patients acquire this illness after a post viral infection or after an Influenza vaccination. As you know, this illness received its 'infamous' name after an outbreak at Incline Village and is associated with various 'hot spot' outbreaks throughout the world over the preceding decades. It is associated with a one or more pathogens as the trigger.
I just recently ran across an article that pique my interest. Most researchers are now reconsidering it could be an neuroimmune or autoimmune disease or disorder.
This article indicates that a pathogen H1N1 or an influenza vaccination is a cause of an autoimmune disease. It could be a subset of ME patients or it could lead to a dead end but I thought it would be worth exploring before posting a thread on it. It could be controversial.
So I went looking and it was a fortuitous event that I just happened to read an
NBC News Article from
Reuters concerning children in young adults developing an irreversible sleep disorder from the adjuvant that was in the vaccine manufactured by GlaxoSmithKline...sounds like a law firm.
.
Flu shot ingredient eyed for narcolepsy link
Some Northern Europe countries used a particular flu vaccination against the H1N1 2009 strain called Pandemrix which triggered an irreversible sleep disorder in some children (1/16,000 vaccinations in Finland, a 5-13 fold increase risk).
I considered this very interesting but I didn't know why a sleep disorder would be irreversible so I went hunting on PubMed and happened to come across research center that is doing research in this field. The information was astounding. The sleep disorder is called narcolepsy. I assumed it had to do with people who had sleep apnea, obesity or trouble sleeping because of snoring. It doesn't have anything to do with sleep issues per se. There is a psychiatric component to this disorder which I am not referencing but only the neurological disorder. The DSM-5 manual lists it as narcolepsy/hypocretin.
I came across some research where individuals that have a certain genetic predisposition can acquire this autoimmune disease. It attacks the neuropeptide Hypocretin located in the Hypothalamus and wipes them out.
Hypocretin controls the sleep/awake state and the circadian rhythms as well as the homeostasis of the entire human body!
A mutated gene in the HLA(human leukocyte Antigen) is associated with MS. About 70% of the patients with multiple sclerosis have HLA-DR2 gene.
Another pathogenic trigger H1N1 is associated with another autoimmune disorder located in the same region Over
90% of patients with narcolepsy-cataplexy carry
HLA-DQB1*0602 mutated gene expression.
Research had found that
narcolepsy is an autoimmune disease that
destroys the
neuropeptide Hypocretin located in the Hypothalamus within the brain. Hypocretin and/or receptors OXi1 and Oxi2
control the entire body's asleep and awake state as well as circadian rhythms. Furthermore, it
down regulates the HPA Axis, muscle... olfactory, inability to adjust to temperature extremes, severe insomnia, brain fog and memory issues, POTS, blood pressure volume, cardiovascular issues basically the human homeostasis...Occam's razor!
It is caused by a
gene mutation through an exposure to an influenza pathogen. This can be
passed on genetically to other generations. Not every one that has this mutated gene develops this condition but
90% of the people who do have narcolepsy vs. controls have this
gene mutation in the HLA ( Human Leukocyte Antigen) It is near the same location as a
mutated gene expression for MS!
What if the immune system targets this pathogen but also mistakes proteins in the brain that regulate sleep/awake cycles as a pathogen and take them out as well? Research has shown that this is what exactly occurs in narcoleptic patients?
So what if the immune system was killing cells that produce hypocretin? Hypocretin (orexins) are molecules
found only in the hypothalamus and had some weak resemblance with the gut hormone secretin. Only 10,000-20,000 cells in the entire human brain (out of many billions) secrete these specific hypocretin molecules.
HLA antigens are molecules produced by the HLA genes and HLA molecules which are expressed on the surface of white blood cells to coordinate the immune response and DR and DQ are two different types of HLA molecules.
We know that HLA genes are very important systems to keep the immune system in check. The HLA molecules are very particular in that different individuals generally carry different
HLA "subtypes" (for example DR1, DR2, subtypes of HLA-DR; DQ1, DQB1*0602, subtypes of HLA-DQ).
The fact HLA molecules are slightly different from one individual to another makes our immune system slightly different from each other.
The immune system uses HLA to differentiate between “self” cells and foreign cells (and attacks those presented as foreign), and most autoimmune diseases are associated with variants of HLA!
T
here is two ways to find this disease in a patient, CFS or by DNA Testing. So I talked to genetic researcher involved with this research. You can be tested for this. This researcher had no idea to look at the ME/CFS patient population! So I asked him to look at the research conducted by of CFS spinal fluid conducted by
Natleson et al. here: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0017287 and Smith et al. Lyme patients here:
http://tinyurl.com/a4qtnxb on distinguishing ME and Lyme patients to determine if there was any absence of Hypocretin in the CFS of patients.
Research has found that after following specific influenza flu infections, the immune system
confuses a portion of the flu virus with hypocretin related proteins, destroying the 10-20,000 neurons in the brain that produce hypocretin.
In recent studies, more than 90 percent of sleep disorder patients were shown to carry one such variant which is now
considered an autoimmune disease.
https://en.wikipedia.org/wiki/Excessive_Daytime_Sleepiness
So you have disease produce by a viral pathogen that mimics many of the symptoms of ME/CFS patients. I don't know if it is something people haven't looked into for one reason or another but the only way they can determine if it is an autoimmune disease is whether hypocretin is missing in the CFS of patients thus the question on the proteins found in the PlosOne study in patients with ME/CFS. There is also one other way, by DNA genetic testing, that locates the mutated gene expression within patients.
Vaccines and influenza H1N1 can cause this condition as mentioned before. Other threads on here about EDS and mercury amalgams are not noted for infectious hot spots in various parts of the world over the last few decades which gave rise to ME/CFS.
Could be a subset but patients should be aware of it for diagnostic purposes?
When the autoimmune system attacks the virus, it also attacks the hypocretin. I found out that it affects the HPA axis, gut issues, blood volume and pressure, it is genetically passed down.
It is very similar to MS and Parkinson, sensitivity to smell, affects the heart cardiovascular system, dysautonomia, POTS.
Orexins (hypocretins) are neuropeptides primarily localized in the hypothalamus and are implicated in the regulation of a variety of activities, including feeding behavior and energy balance. Orexins have also been found to be linked to idiopathic narcolepsy (excessive daytime sleepiness). Two homologous peptides, orexin-A (OXA) and orexin-B (OXB), are proteolytic cleavage products derived from a common precursor called prepro-orexin. Prepro-orexin is expressed in a specific population of neurons in and around the lateral hypothalamic area and is involved in the catecholaminergic and serotonergic feeding systems, playing a role in circadian feeding, sex differences, in feeding and spontaneous activity. Prepro-orexin mRNA level is up-regulated upon fasting, suggesting a physiological role for the peptides as mediators in the central feedback mechanism that regulates feeding behavior. Orexin expression is not obviously related to changes in body weight, insulin or leptin, but is stimulated under conditions of low plasma glucose in the absence of food. OXA and OXB are 33- and 28-residue peptides, respectively, and were first isolated from rat hypothalamus. OXA is completely conserved among human, rat, mouse, and bovine species and is found in the endocrine pancreas. Fasting activates OXA neurons in the lateral hypothalamic area and gut.
Narcolepsy with hcrt deficiency is now known to be associated with a Human Leukocyte Antigen (HLA) and T-cell receptor (TCR) polymorphisms, suggesting that an autoimmune process targets a single peptide unique to hcrt-cells via specific HLA-peptide-TCR interactions. Recent data have shown a robust seasonality of disease onset in children and associations with Streptococcus Pyogenes, and influenza A H1N1-infection and H1N1-vaccination, pointing towards processes such as molecular mimicry or bystander activation as crucial for disease development. We speculate that upper airway infections may be common precipitants of a whole host of CNS autoimmune complications including narcolepsy.
Since active pathogens are not discernible in blood serum,
what if this is an autoimmune disease or disorder?
What if these pathogens either bacterial/viral/fungal is the trigger point for a host of fatiguing autoimmune disorders dependent upon the genetic predisposition of a person? So if a patient has a gene mutation in the HLA gene allele region of the brain that attacks any of the hypocretin molecules or their receptors, it is ME/CFS or Narcolepsy or Multiple Sclerosis or Lupus etc. depending upon the location of a mutated HLA gene? Does this make any sense to you?
Genetic testing should indicate gene mutations in these regions of ME/CFS patients.
I talked to the Stanford Researcher and Geneticists Dr. Joachim Hallmayer and asked him if another pathogen or even if H1N1 could just wipe a portion of the hypocretins and not all of them; he stated it was a possibility. All narcolepsy patients show a 90% variant of the HLA gene.
Perhaps that is why research is unable to find this disease in ME/CFS since it only affects people who have a genetic predisposition to a pathogen consisting of viral/ bacterial/fungal pathogen that attacks all or a portion of the hypocretin molecules or receptors that govern circadian rhythms and the sleep/awake cycle.
This is why patients experience crippling fatigue but at night suffer from insomnia and are unable to sleep. There is a lot of discussion on the forums concerning sleep medication. I was also reading a blog concerning a woman from Australia who collapses suddenly when she shops.
Dr. Hallmayer indicated they have not researched this area concerning ME/CFS patients nor researched whether other genetic defects could cause the depletion of the hypocretin molecules.
RESEARCH ARTICLES:
Orexins control intestinal glucose transport by distinct neuronal, endocrine, and direct epithelial pathways
A patient with both narcolepsy and multiple sclerosis in association with Pandemrix vaccination.
Narcolepsy with cataplexy is caused by a selective loss of hypocretin-producing neurons, but symptomatic narcolepsy can also result from hypothalamic and brain-stem lesions caused by multiple sclerosis (MS). We report a previously healthy man who developed clinical and laboratory verified narcolepsy without having any indication of hypothalamic lesions and MS after vaccination against the influenza H1N1 with Pandemrix. HLA typing showed both DRB1*15:01, associated with MS and DQB1*06:02, associated with narcolepsy. The genetic susceptibility in this patient makes it tempting to speculate upon an immune-mediated mechanism and a common etiology for both diseases in this patient.
Narcolepsy with hypocretin/orexin deficiency, infections and autoimmunity of the brain.
Attenuated heart rate response is associated with hypocretin deficiency in patients with narcolepsy
Effects of ambient temperature on sleep and cardiovascular regulation in mice: the role of hypocretin/orexin neurons.
Sleepiness at the time of testing impairs olfactory performance.
A missense mutation in myelin oligodendrocyte glycoprotein as a cause of familial narcolepsy with cataplexy. Constant falling down or weakness in the legs.
A HUNDRED YEARS OF RESEARCH at Stanford Research
Selected Publications Stanford Research
You can Google “streptococcal hypocretin” or Google “influenza h1n1 hypocretin”
At any rate, the hypothesis is being communicated to Mady Hornig to explore.
Eco