As much as we would all like to believe it,the immune anomalies in autism,have not pointed to a distinct syndrome,like lupus or a primary immune deficiency,which is what doctors look for.

I spent nearly ten years being tested for every possible form of immune disease,and I did not have any of them.And I had a very suggestive history of immune disease.Recurring meningitis,and pneumonia,rheumatic fever,and a chronic lung infection that lasted nearly twenty years.

Interleukin-10 is associated with resistance to febrile seizures: Genetic association and experimental animal studies.

IL-10 is found to be protective of seizures.

Elevated cytokine levels in children with autism spectrum disorder

Children with autism are found to have less il-10 at baseline than their undiagnosed peers. Another study in 2009 found unchanged levels of IL-10 in the brains of children with autism.

The role of interleukin-1beta in febrile seizures.

One of many studies showing a relationship between increased levels of IL1-Beta and genesis of febrile seizures.

Preliminary evidence of the in vitro effects of BDE-47 on innate immune responses in children with autism spectrum disorders

Blood cells from with autism are found to generate more IL1-beta than controls when the blood is pretreated with BDE-47 and then stimulated with LPS. Additional tnf-alpha creation is also observed, which we know is critical towards succeptibility of seizure generation by early LPS exposure.

Proinflammatory and regulatory cytokine production associated with innate and adaptive immune responses in children with autism spectrum disorders and developmental regression

83% of ASD cases generated IL-1beta and TNF-alpha more than 2 SD above the mean when stimulated with LPS. Other stimulators revealed large increases in TNF-alpha in the autism group compared to the control group. This same researcher group found decreased IL-1beta when testing subgroups of autism and using slightly different methods of stimulation.

– pD

“Absent biomarkers, well-defined risk factors, or large effect sizes, the committee cannot rule out, based on the epidemiological evidence, the possibility that vaccines contribute to autism in some small subset or very unusual circumstances. However, there is currently no evidence to support this hypothesis either.”

By the way, it just so happens that having a postnatal inflammatory response during critical developmental timeframes leads to increased succeptibility to seizures into adulthood in an animal model. What a strange coincidence!

http://www.jneurosci.org/cgi/c.....28/27/6904

I particularly appreciate the quote in the discussions section:

The most exciting finding of the present study is that a mild inflammatory response evoked by LPS during a critical period of development causes a long-lasting increase in hippocampal excitability in vitro, and enhanced seizure susceptibility to the convulsants LI-PILO, KA, and PTZ in vivo. The latter effect was observed over a range of mildly inflammatory doses of LPS and was only evident if administered during the second postnatal week (P7 and P14), and not before (P1) or after (P20) this time. Importantly, inactivation of the proinflammatory cytokine TNF with an intracerebroventricular TNF antibody blocked the long-term changes to seizure susceptibility induced by LPS, whereas intracerebroventricular administration of rrTNF alone mimicked the effect of LPS on seizure susceptibility. These novel results indicate that a single transient inflammatory episode during development can modify the brain through a TNF-dependant mechanism, making it more susceptible to generate seizures in adulthood.

Several particularly pertinent points here regarding an association to an inflammory immune response:

1) We are quickly ammassing evidence that we can safely disregard the notion that there is no available mechanism by which immune responses can alter neurological functioning. In the case of the study above, we see that a single immune response can infer lifelong changes to neural excitability. Further, the response need not be significantly large, as the authors report that the results were evident with ‘mildly inflammatory doses of LPS’.

2) The rats didn’t get an actual infection, just the protein components of bacterial walls, LPS. The authors were able to duplicate the same symtpoms by injecting inflammatory cytokines. The authors were able to remove increased succeptibility by concurrently adminitering tnf alpha blocking agents. In other words, the immune response was responsible for generating increased succeptibility to seizures.

3) There was a critical early life window during which generation of such an immune response could generate increased succeptibility to seizures. It seems appropriate to mention the obvious; over the past two decades we’ve seen a gradual decrease in the of first vaccinations, and an increase in the number of vaccinations given at that lower age.

4) Once again, the impact of an immune response is invisible to all of our thimerosal based studies. Likewise, studies involving the MMR constitute an analysis of a small subset of our vaccination schedule. Without these two types of studies there are zero studies involving autism and vaccination.

– pD

http://www.ncbi.nlm.nih.gov/pubmed/17555525?

This was a population based study which showed that 7.1% of infants referred for diagnosis and treatment in Iceland for neonatal seizures had an AS diagnosis. The prevelance of ASD’s in this group is more than 10 times greater than the CDC’s latest estimate of 1/150 (.667) prevelance for ASD in 8 year old children in the US, a prevelance rate that is inflated by the the phenomena of diagnostic substition
present in the CDC statistics.

I assume you can supply documentation for this.

I’m don’t know you well enough to know if your question is geniune or not; that is, do you already know such research exists, and ask anyways? In any case, here are a couple.

http://pediatrics.aappublicati.....122/2/e438 [Highly increased levels of MIF found in autism, with circulating levels correlating with autism severity. Other populations with increased levels of MIF include asthmatics, and those with type 1 diabetes.]

From the paper:

MIF is encoded in a functionally polymorphic locus on chromosome 22q11.2 (Online Mendelian Inheritance in Man No. 153620, GenBank accession No. NM_002415) that has been associated with the incidence or severity of different autoimmune inflammatory conditions.37 Given its location in a previously identified locus of interest and its upstream action in immunity, MIF may represent a candidate gene for ASD or its components. Thus, the central hypothesis underlying this research was that a genetic predisposition to a particular level of MIF production may lead to a proinflammatory profile of cell activation that, if present during a neurodevelopmentally sensitive period, might contribute to the etiopathogenesis of autism.

http://www.ncbi.nlm.nih.gov/pu.....d_RVDocSum [Significantly decreased levels of TGF-Beta1 are identified in autism, again, with a correlation between circulating levels and severity. TGF-Beta1 plays an important role in regulating immune responses. This is the second paper reporting decreased levels of tgf-beta1 in autism.]

http://www.ncbi.nlm.nih.gov/pu.....d_RVDocSum [Significant decreased of p-selectin are found in autism population, with correlations to autism severity. P-selectin is a component involved with transport of lymphocytes out of the bloodstream and into the surrounding tissues.]

In any case, there are lots, lots more, but space is an issue, but these are several that also include correlations between the level of abnormal measurements and behavioral severity.

Finding “connections” with autistics and abnormal immune behavior(s) will take more than a partial observation from any one or the few studies that have made them.

Well, if I felt like spamming this post like crazy, I could probably post two dozen studies on abnormal immune functioning in autism. Maybe more.

What is completely lacking (a glaring, gaping hole) is the mechanism of autism as a consequence of immune response/dysfunction.

Aha. Well, I’d really love to get a more detailed question from you here; what would keep me from saying the same thing about any number of genetic associations. I wouldn’t, of course, but my point is that we really don’t understand enough of what is driving autistic behaviors at all; any area of research is subject to this claim.

In any case, we do actually have evidence that immune responses can alter neurological functioning.

http://www.ncbi.nlm.nih.gov/pu.....d_RVDocSum

From the abstract:

“In inflammatory diseases occurring outside the CNS, communication between the periphery and the brain via humoral and/or neural routes results in central neural changes and associated behavioral alterations. . . Our results identify the existence of a novel immune-to-CNS communication pathway occurring in the setting of peripheral organ-centered inflammation which may have specific implications for the development of alterations in cerebral neurotransmission commonly encountered in numerous inflammatory diseases occurring outside the CNS.” [snipping due to space considerations]

It should be noted that highly increased TNF-alpha and MCP-1 have already been observed in the CNS and brain of autism populations (Chez 2007 / Vargas 2005).

Here is one regarding depression:

http://www.ncbi.nlm.nih.gov/pu.....d_RVDocSum

Interestingly, depressed patients with increased inflammatory biomarkers have been found to be more likely to exhibit treatment resistance, and in several studies, antidepressant therapy has been associated with decreased inflammatory responses. Finally, preliminary data from patients with inflammatory disorders, as well as medically healthy depressed patients, suggest that inhibiting proinflammatory cytokines or their signaling pathways may improve depressed mood and increase treatment response to conventional antidepressant medication. [Again, snipping due to space considerations]

You are characterizing our understanding of the interactions between the immune system and neurological functioning, including autism, as well understood. I am taking the opposite approach.

A state of chronic inflammation would likely result in disturbances to critical formation processes (i.e., MET).

The fact remains, EVERY SINLGE PHYSIOLOGICAL FUNCTION IN OUR BODY HAS AN IMMUNE COMPONENT OR RELATIONSHIP INVOLVED

You are correct. So I’m wondering why this means that in the case of autism we should not give weight to exceedingly abnormal values that have been observed? I believe this speaks towards my point more than your own; it is critically implicated all of the body, has been found to be skewed in dozens of studies, but yet, you are yet to be convinced of its importance.

Look at the research that talks about the mechanisms that are known about why autistics are autistic, and what dysfunctions they have in there brain chemistry.

Hm. Well, presumably you have documentation that these particular dysfunctions in brain chemistry are causative of autism, as opposed to resultant? I’d love to see those.

In any case, your assertion is again incorrect.

What about glutamate processing; implicated by highly increased levels that have been observed in autism, as well as genetic studies that show assocations between polymorphisms and processes eventually responsible for glutamate processing. Well, it turns out, we have evidence that an abnormal immune response can result in altered glutamate metabolism, and indeed, dysregluation of a vareity of amino acids.

http://www.ncbi.nlm.nih.gov/pubmed/18567974

There are many others. Instead of spamming away, maybe you should tell me which particular components of brain chemistry you feel are the ones causing autism, and we can see if there is an immune component.

Then, try to work up a link to inflammation/immune responses.

OK.

http://www.ncbi.nlm.nih.gov/pu.....rom=pubmed

PURPOSE: Early-life seizures increase vulnerability to subsequent neurologic insult. We tested the hypothesis that early-life seizures increase susceptibility to later neurologic injury by causing chronic glial activation. To determine the mechanisms by which glial activation may modulate neurologic injury, we examined both acute changes in proinflammatory cytokines and long-term changes in astrocyte and microglial activation and astrocyte glutamate transporters in a “two-hit” model of kainic acid (KA)-induced seizures. METHODS: Postnatal day (P) 15 male rats were administered KA or phosphate buffered saline (PBS). On P45 animals either received a second treatment of KA or PBS. On P55, control (PBS-PBS), early-life seizure (KA-PBS), adult seizure (PBS-KA), and “two-hit” (KA-KA) groups were examined for astrocyte and microglial activation, alteration in glutamate transporters, and expression of the glial protein, clusterin. RESULTS: P15 seizures resulted in an acute increase in hippocampal levels of IL-1beta and S100B, followed by behavioral impairment and long-term increases in GFAP and S100B. Animals in the “two-hit” group showed greater microglial activation, neurologic injury, and susceptibility to seizures compared to the adult seizure group. Glutamate transporters increased following seizures but did not differ between these two groups. Treatment with Minozac, a small molecule inhibitor of proinflammatory cytokine upregulation, following early-life seizures prevented both the long-term increase in activated glia and the associated behavioral impairment. CONCLUSIONS: These data suggest that glial activation following early-life seizures results in increased susceptibility to seizures in adulthood, in part through priming microglia and enhanced microglial activation. Glial activation may be a novel therapeutic target in pediatric epilepsy.

So. If you induce seizures in early life in rats, they go on to develop abnormal behaviors, a state of activated microglia, and an increased succeptibility to seizures in adulthood. If you want to prevent these things from happening, you can do so by interferring with the proinflammatory immune response. Hiyo!

Do I really need to post links to findings of chronically activated microglia, increased presence of seizures, and abnormal behavioral functioning in autism? Do I?

In the past twenty years we have undertaken a course wherein we insure that more and more of our infants experience early life seizures as the result of vaccinations. It just so happens, that doing so seems to create behavioral and physiological characteristics of autism. This effect is completely invisible to every single autism / vaccine study thus far undertaken.

So far, I’ve seen nothing.

What about now?

– pD

“I’ve just banned Harold. I simply couldn’t be bothered reading through one more pompous little missive.”

YAY! You’ve just made my day! I wish ALL of the Hub was a Best and Doherty-free zone.

I assume you can supply documentation for this.

First off, Harold, just because some say could and should doesn’t mean it is. We could/should look at sub-populations…yeah, we can/should. It’s called science. But because someone says we should look, this isn’t proof either way. It is merely a statement recommending a possible course of action. To take anything else from those statements you’ve provided is a step beyond jumping to conclusions. Do yourself a favor (be objective), take only what was actually said from the statement and stop deriving unfounded conclusions.

pD,

Finding “connections” with autistics and abnormal immune behavior(s) will take more than a partial observation from any one or the few studies that have made them. What is completely lacking (a glaring, gaping hole) is the mechanism of autism as a consequence of immune response/dysfunction. The fact remains, EVERY SINLGE PHYSIOLOGICAL FUNCTION IN OUR BODY HAS AN IMMUNE COMPONENT OR RELATIONSHIP INVOLVED. The vaccine cause autism camp have yet to provide any credible mechanism. Some have been tried, but they hopelessly feeble, and they are dropped and they come up with another a few days later.

Look at the research that talks about the mechanisms that are known about why autistics are autistic, and what dysfunctions they have in there brain chemistry. Then, try to work up a link to inflammation/immune responses. You will see why the concept of autism as a result of immune dysfunction has little traction.

The world is waiting for the mechanism behind autism and vaccine/immunity. So far, I’ve seen nothing.