What do molecular mimicry, the H1N1 Flu vaccine and the HPV vaccines Gardasil or Cervarix have to do with the brain neurons involved in narcolepsy or hypersomnia? Plenty. Researchers are learning that vaccine induced immune reactions can destroy innate cells via molecular mimicry and in the case of the flu vaccine, the hypocretin/orexin neurons responsible for maintaining wakefulness are attacked. Idiopathic hypersomnia, a derivative of narcolepsy is one of the many side effects reported by post Gardasil girls and women. Could the HPV vaccine be attacking those same neurons? Is molecular mimicry at play in the HPV vaccine too? The answers are yes and possibly, but with the HPV vaccine, the molecular mimicry is more widespread and the research only beginning to delineate its effects.
What is Molecular Mimicry?
Molecular mimicry is the notion that foreign pathogens like bacteria, viruses and vaccines can be so similar in structure or function to innate, ‘self’ peptide sequences that they evoke an autoimmune response in the exposed individual. Molecular mimics are thought to be involved in the onset of Type 1 Diabetes, Lupus, Multiple Sclerosis and other diseases, including some neurological disease processes.
Molecular mimics are snippets of protein code embedded within the pathogen that are either functionally similar and contain sequences of identical code to those found innately in humans, or structurally similar and because of their shape can bind to and activate an immune cell receptor. The protein codes, called motifs, are instructions that govern all aspects of the cell’s activity levels, and indeed, our very health and survival. Some codes tell the cell to live and how to function, others tell the cell to die and even how to die. The thought is that when external pathogens contain protein motifs that mimic internal and innate protein motifs, our immune system recognizes the foreign invader and attacks not only the dangerous pathogen, but the innate molecules that contain those same protein motifs too, evoking all sorts of damage to potentially many different tissues and organs. When there is structural similarity between the pathogen and immune cells, the process for immune activation is quite easy. The pathogen slips in, binds to a receptor and initiates the inflammatory immune response. In either case, the immune response to the environmental pathogen results in a disease process identified as autoimmune – the immune system attacking itself. It should be noted that connection between molecular mimicry and autoimmune disease onset is hotly debated.
Narcolepsy or Hypersomnia, the Immune System and the Flu Vaccine
In 2010, amidst the fears of the H1N1 swine flu pandemic, citizens in Scandinavia and Europe were given the adjuvanted (MF-59 a squalene based adjuvant plus ASO3 – squalene-α-tocopherol mix) flu vaccine called Pandemrix. Shortly thereafter physicians began noting an increase in new onset cases of narcolepsy, especially in Scandinavian children.
Narcolepsy is the lifelong disorder characterized by excessive sleepiness with abrupt and sudden transitions to REM sleep. It affects approximately ~ 1 in every 3000 individuals worldwide. Individuals with narcolepsy/hypersomnia have sudden and very strong urges to sleep throughout the day, though at night insomnia may develop. Patients may fall asleep as many as 20-30 times per day, for brief periods, making regular functioning difficult without wake stimulating medications.
Often co-occurring with narcolepsy is a condition called cataplexy. Cataplexy denotes the muscle tone and behavioral changes that precede the narcoleptic sleep incident. Cataplexy symptoms can range from the barely perceptible loss of facial muscle tone or twitches to full muscle paralysis and collapse. Approximately 70% of patients with narcolepsy also have cataplexy.
Hypersomnia, or more specifically, idiopathic hypersomnia, is a central nervous system disorder similar to narcolepsy. Like with narcolepsy, the brain is unable to regulate sleep-wake cycles, only here instead of bouts of uncontrollable sleepiness and periods of sudden onset sleep, with idiopathic hypersomnia, the sleepiness is severe, excessive and continuous. Both narcolepsy and idiopathic hypersomnia have long been thought to be autoimmune in nature, triggered by environmental factors. Bacterial infections such as streptococcus pyogenes, the bacteria responsible for strep throat/pharyngitis and skin infections like impetigo can elicit narcolepsy in some individuals, as well as autoimmune rheumatic fever and kidney disease in others.
Hypocretin/Orexin Neurons Damaged in Patients with Narcolepsy/Hypersomnia
From an autoimmune standpoint, key to triggering narcolepsy in some individuals, is presence of a particular gene variant in immune cells called human leukocyte antigens (HLA). The variant is labeled HLA -DQB1*0602. Fully 98% of patients with narcolepsy exhibit the DQ0602 haplotype (DQA1*0102/DQB1*0602) versus 18-25% of the general public who have the mutation but do not experience narcolepsy. DQ0602 impairs and often destroys the brain neurons that secrete a peptide hormone that is required to maintain wakefulness. The wake-promoting hormone released from the hypothalamus, is called orexin or hypocretin. Orexin and hypocretin are the same molecule that was discovered simultaneously by two separate research groups and then named independently. Readers will see research articles on both orexin and hypocretin linked to narcolepsy (and the flu vaccine, migraine, glucose metabolism, feeding behavior, to name but a few other areas of research).
Molecular Mimics in the Flu Vaccine Attack Hypocretin Neurons and Induce Narcolepsy
Researchers from Stanford found molecular mimics in the adjuvanted Flu vaccine, Pandemrix, both sequence code and structural similarities that initiated immune system attacks on the hypocretin/orexin system in narcolepsy patients but not healthy controls. It should be noted in this particular study, only the adjuvanted version of the flu vaccine was studied, as that was the product distributed in Europe and Scandinavia. The non-adjuvanted version of the Flu vaccine sold in the US was not tested.
For the present study: CD4+T Cell Autoimmunity to Hypocretin/Orexin and Cross-Reactivity to a 2009 H1N1 Influenza A Epitope in Narcolepsy, the researchers used confirmed narcolepsy patients and controls who were all positive for the DQB1*0602 gene variant associated with narcolepsy. Here, despite having the variant, only the patients had a reactivation of the immune attack on the hypocretin neurons. The control group, who were also positive for the variant, but who had no active symptoms or diagnoses of narcolepsy, did not demonstrate the same immune response. This suggests that other factors in addition to the molecular mimics and a personal predisposition must align to initiate the immune response or, in this case, what is deemed the autoimmune response. It also suggests, that in predisposed individuals, vaccine introduced molecular mimics can trigger immune system attacks and initiate disease states that may or may not have been symptomatic pre-exposure.
What this research does not explain is whether the new onset cases observed in the Scandinavian population post vaccine exposure were solely in individuals with the pre-disposing genetic variant. Was the increase in narcolepsy post flu vaccine exposure indicative of a latent disease state simply triggered by the vaccine? Or is it possible that there are other molecular mimics embedded within the flu vaccine, not yet identified, that might also trigger narcolepsy? Finally, and most importantly, could there be additional factors native to this and other vaccines, to the individual, or with the combination thereof, that evoke an attack on the neurons responsible for regulating wakefulness and inducing narcolepsy, or evoke an attack on other cells and elicit different disease processes? If the answer is yes to any of these questions, then our approach to vaccines ought to be rethought.
Molecular Mimicry and the HPV Vaccines Gardasil and Cervarix
Here is where it gets interesting for those interested in post Gardasil injury. The flu study, as limited and focused as it was, provides important clues to how and why the HPV vaccine might also induce an array of side effects, including, but not limited, to hypersomnia in some individuals but not in others.
Researchers have begun investigating molecular mimics in the HPV vaccines Gardasil and Cervarix. Thus far, they have identified 82 pentamer (5) level mimics and 34 heptamer (7) level mimics in the HPV 16L component. The offending motifs control a variety of cell behaviors related to cardiac functioning, cell permeability and cell death. An immune system attack on any of these motifs could elicit serious illness. Indeed, the researcher postulates that the mimicked motifs controlling cardiac functioning could be culprits in the post HPV vaccine incidences of sudden death.
To my knowledge, the full HPV vaccine to human proteome has not been mapped and so how or if there are mimicked protein motifs within the HPV vaccine that are capable of attacking the hypocretin/orexin neurons is not known. Nevertheless, idiopathic hypersomnia, a derivative of narcolepsy, is one of the core symptoms of post Gardasil injury, though it is sometimes misdiagnosed and mischaracterized as excessive fatigue and sleepiness. Additionally, a number of other symptoms post Gardasil are influenced by the hypocretin/orexin system, including feeding behavior, gastroparesis (perhaps via galanin) migraine, and all over pain (via dynorphin) – more on this in subsequent posts. Since we now know that molecular mimics can evoke reactions, it is only a matter of time before researchers match the vaccine protein motifs and structural homologies to individual gene variants, environmental predispositions and the clinical symptoms/syndromes that develop.
Perhaps even more interesting, when we dig into the hypocretin/orexin system we see that the neurons are especially susceptible to changes in ATP. Intracellular ATP in hypocretin/orexin neurons must be maintained at much higher levels than in other cells. Diminished ATP stores inhibits hypocretin/orexin firing and thereby reduces sustained wakefulness. We know from other research and patient reports that severe thiamine deficiencies are present in post Gardasil injury (whether the deficiencies existed pre-Gardasil, but were asymptomatic is not clear). Thiamine is a required co-factor in the production of ATP. Reduced thiamine would impair functioning in the hypocretin/orexin neurons and induce the hypersomina and hypophagia and many of the other symptoms we see post vaccine.
In subsequent papers, I will explore the myriad functions the hypocretin/orexin neurons regulate and how damage to those neurons, either directly as indicated in the flu vaccine study, or indirectly, via targeting critical co-factors provides clues to the constellation of post Gardasil injuries. Additionally, I will address the molecular mimicry debate and how it will reshape the framework for understanding autoimmunity.
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This article was published previously in January 2014.