Saturday, July 21, 2012

Read Between The Lines

A very interesting study was just released that showed that disruptions of the immune system can lead to the behaviors of autism, at least in mice.  There are quite a few write ups of the actual results, such as herehere, here, or here, so I won't try to add anything to these already good reviews.

Instead I want to go for gross oversimplification of the findings because the pattern it suggests is, in my humble opinion, a good guide to what autism actually is for many people.  Ready?

1. Mother's immune system is given a swift kick.
2. Child's immune system is thrown out of balance.
3. Child develops behaviors of autism later in life.

and, most importantly -

4. Correcting the child's immune system reduces the autistic behaviors.

Of course this is all in mice and doesn't automatically translate into humans.  But given all of the evidence of immune disruptions in autism I strongly suspect that we will see some effective evidence based therapies for autism that target these disruptions within the next ten years.

You can call this pattern anything you want but the key elements are that something is biologically out of balance in people with autism and that correcting the imbalance can lead to "recovery" from autism.

Read that last sentence again because I feel that it is the key to putting together all of the things we know about autism. Instead of the current idea that autism is a fundamental part of who a person is (i.e. it is written into their genetic code), this model suggests that autism is a state that a person's body is in. There is still room for genetic mutations in this model but these mutations are important insofar as they make it easier for a person to get into a disrupted state.

I could write pages and pages about how this model fits into what we know about autism but since I don't have that much time nor I am not under the delusion that anyone would actually want to read that, I will just quickly hit the highlights.

1. The "genetic" model of autism is a bust.  There is no single mutation or group of mutations that occur in any sizable part of the autism population.  The mutations that have been found can be significant for the people who have them but I think they are really just background noise in the larger discussion of what causes autism.

2. The number of people with autism is increasing rapidly.  There are a number of reasons for this increase but it isn't really possible to deny that there has a real and substantial increase in the number of people who have autism.

3. There are many, many, many biological disruptions that are seen in substantial subsets of people with autism.  I always have to laugh when people dismiss these disruptions as unimportant (or "co-morbid") because they only appear in like 30% of people with autism and then turn around and trumpet the latest genetic finding as significant when it appears in maybe 1% of people with autism.

4. There is substantial evidence from other related conditions, such as Retts, Fragile X, SLOS, Wilsons disease, and the group of conditions called inborn errors of creatine metabolism (just to name a few), that correcting the biology corrects the condition even when there are genetic mutations present.

All of these ideas fit nicely into the model of autism as a biological disruption.

You don't have to have some genetic mutation that is "causing" autism, all you need something strong enough to push a person out of equilibrium.  And something that is strong enough to do that could likely cause the random but almost unique mutations that are seen in autism.

The number of people with a specific genetic disorder isn't likely to change rapidly but biologically induced disorders certainly can and do.  If you want a model of that consider Pink's disease.  It came, it rapidly rose, and then, once the cause was found, it disappeared just as quickly as it appeared.

The same can be true for the autism epidemic if get our collective heads out of our asses and stop thinking of autism as some permanent thing and instead consider it as an imbalance that can and should be corrected.

(Before anyone decides to leave a less than polite comment suggesting that I am calling people with autism defective, calling them less than typical people, or wants to suggest that I don't like my children, don't waste your time.  I am not saying, implying, or suggesting anything of the sort.  If you want to interpret my words to mean that then you are certainly entitled to your opinion, but I will ask you to take your stupidity elsewhere.  Serious comments - even if you want to tell me I am completely wrong - are always welcome. )

Thursday, July 5, 2012

Study : Yet Another Immune System Abnormality in Autism

A new study has reported that a large number of children with autism may have an elevated level of interleukin-17A.  This isn't a new result but it is interesting because this time there appears to be an association between the level of IL-17A and the severity of autism - the more severe the case, the higher the level of IL-17A.

If you are interested in the subject I suggest you read the (open access) paper.  It has some good background material about other immune system abnormalities that have been found in autism.

The one thing that I would like to point out is that this elevated level of IL-17A was seen in almost half of even a moderate sized group children with autism - 22 out of 45.  Compare that size and number to what passes for significance on the genetics side of autism research where finding 3 or four children with similar mutations out of a group of thousands is considered significant.

The abstract is below.

Elevated serum levels of interleukin-17A in children with autism.
Al-Ayadhi LY, Mostafa GA.

BACKGROUND:
The T-helper (Th)1/Th2 dichotomy dominated the field of immune regulation until interleukin (IL)-17-expressing T cells (Th17) were proposed to be a third lineage of helper T cells, the key players in the pathogenesis of autoimmune disorders. Autoimmunity to brain tissue may play a pathogenic role in autism. IL-17A is a pro-inflammatory cytokine that has been shown to play an important role in various autoimmune neuroinflammatory diseases. The aim of this study was to measure serum levels of IL-17A in relation to the degree of the severity of autism.

METHODS:
Serum IL-17A levels were measured by ELISA in 45 children with autism and 40 healthy matched healthy controls.

RESULTS:
Children with autism had significantly higher serum IL-17A levels than healthy controls (P <0.001), with increased serum levels of IL-17A found in 48.9% of the autism group. Patients with severe autism had significantly higher serum IL-17A levels than those with mild to moderate autism (P = 0.01), and raised serum IL-17A levels were significantly more common in children with severe autism (67.9%) than in those with mild to moderate autism (17.6%), P = 0.001.

CONCLUSIONS:
Serum IL-17A levels were raised in the group with autism, and the levels correlated significantly with the severity of autism. This is the first study to measure levels of IL-17A in relation to the severity of autism, to our knowledge. Further research, with a larger subject population, is warranted to determine whether the increase of serum IL-17A levels plasma has a pathogenic role in autism, and whether anti- IL-17A therapy could be useful.


References
Al-Ayadhi LY, Mostafa GA. Elevated serum levels of interleukin-17A in children with autism. J Neuroinflammation. 2012 Jul 2;9(1):158. [Epub ahead of print] PubMed PMID: 22748016.