1. Immune System Dysfunction (low levels of immunoglobulin G etc).
"One of our first findings was that immunoglobulin G was much lower in children with autism," Van de Water says. IgG, as it is more commonly called, is an antibody sub-type responsible for the majority of the immune response to invading pathogens.
"This tells us there is likely something wrong in a very basic cell-signaling pathway."
Van de Water and her collaborators also have found that antibody responses to vaccines against bacteria are lower than expected in people with autism, while antiviral responses are fairly normal. This, she explains, was their first clue that the problem lies in the innate immune response – the short-term, non-specific host response to pathogens. Her goal now is to study whether children with autism have autoantibodies to brain proteins and if mothers of children with autism show exaggerated immune responses to proteins in fetal brains.
"We want to know the function of these antibodies during gestation" (UCDavis Medicine, 2007).
Microglia are specifically adapted to sense various types of danger and differentially react with a classical or alternative reparative response. Our understanding of macrophage function has shifted away from focusing on cell lineage to a more systems-based biology of gene networks accomplishing the detoxification and immune functions. With our greater appreciation of microglial involvement in the innate immune response, we have entered a new era in which the modulation of microglia can be proposed as a means of modulating neurological disease (Kofler, J., Wiley, C., 2011).
2. Toxic Stress (oxidative damage, brain inflammation, low glutathione)
So what does all that mean?
Let's look at low glutathione levels in ASD children first. What is glutathione AKA gamma-Glutamylcysteineglycine (GHS): This protein that is made up of three amino acids (cysteine, glutamic acid, and glyceine) is prolific in nearly all the cells in the body, powerful antioxidant, potent anti-viral, anti-cancer agent, detoxifies toxins, promotes the protections of proteins, promotes DNA repair, maintains cellular homeostasis, most notably is maintains normal brain function.
Now that we know what glutathione dose let's look at what suppresses it in the body; acetaminophen (Tylenol) and other pharmaceuticals, acetone, solvents, paint removers, fuels, fuel by-products, heavy metals (mercury (dental amalgams), lead, cadmium, copper, etc.), pesticides, herbicides, nitrates and other food preservatives of chemical origin (in salami, hot dogs, hams, bologna, smoked foods, etc.), artificial sweetener aspartame, benzopyrenes (tobacco smoke, barbequed foods, fuel exhaust, etc.), alcohol, household chemicals (synthetically scented and colored detergents and fabric softeners, air fresheners, mothballs, mildew removers, cleaners and bleach, lawn and plant fertilizers, etc.), housewares chemicals (non-stick coating of pans and skillets, plastic containers and linings of tin cans and other food packaging), formaldehyde and styrene (photocopiers and toner printers), chlorine in treated water, medical X-rays, UV radiation, industrial pollutants (Immune Health Science, 2013). I have highlighted some of the more common elements that we in the autism community associate with vaccine injury, but as you can see our population is inundated with glutathione reducers.
The glutathione redox status is also connected with mitochondrial function (discussed later). And is it not interesting that children who have ASD have a high incidence of mitochondrial dysfunction without the gene mutation, called "acquired mitochondrial dysfunction" (Frye et al., 2013).
Collectively, these studies suggest a critical role for microglia in the innate immune response to CNS pathogens, leading to the activation of adaptive immune functions, most importantly Ag presentation capacity. Microglia have been suggested to play a role in MS, a human T cell-mediated autoimmune demyelinating disease (5). MS has been suggested to be initiated and/or exacerbated by infections, particularly in the CNS (4). Thus, the innate immune response to pathogens infecting the CNS may play an important role in the development and/or exacerbation of the underlying autoimmune response, in which triggering of proinflammatory cytokine production by the microglial innate immune response may play an important role" (Olson, J., Miller, S., 2004).
3. ENERGY METABOLISM (MITOCHONDRIA)
Sub-group 1: Elevated Lactate - mito dysfunction with no underlying gene mutation
Sub-group 2: Elevated AST - oxidative stress rather than impaired mitochondrial function
Sub-group 3: Elevated Alanine/Lysine ratio - mito dysfunction associated with Complex 1 deficiency
Sub-group 4: Elevated Multiple Acylcarnitines - no mito, associated w/ clostridia bacteria
Dr. Frye researched deeper into the abnormal lab findings of each group and found further lab abnormalities that were unique to each sub-group.
Sub-group 1: Elevated urine 2-methyl-3-hydroxybutyric acid, and ammonia
Sub-group 2: Lower urine 5-oxoproline (AKA pyroglutamate, a metabolite involved in glutathione utilization and recovery). May signal glutathione depletion.
Sub-group 3: Elevated alanine and urine pyruvate. Sub-group had a higher rate of epilepsy.
Sub-Group 4: Elevated C5OH, C12, C14, C14:OH and C16 acylcarnitines; not consistent with any known fatty oxidation disorder. Elevated urine 3-OH-3methylglutaric acid; citric acid cycle dysfunction. Sub-group had a higher rate of autistic regression.
Now I can go into demyelination and methylation, which is all tied into these systems and how that impacts neurological disease (autism etc) but I will save that for another day.
To review further: Current science in brain/biological disorders, autoimmunity, and mitochondrial disease in autism.
4. Prenatal exposure to persistent organic pollutants (POPs)
5. MTHFR Dysfunction
6. Co-Occurring Biological Conditions
Our study demonstrated that serum TRX levels were associated with ASD, and elevated levels could be considered as a novel, independent diagnosis indicator of ASD.
Evaluating the weight of peer-review, ASD is presenting as a systemic abnormality creating immune dysregulation/inflammation, impaired detoxification, redox regulation/oxidative stress, and mitochondrial dysfunction. Caused by toxicant exposures with genetic interplay.