Study links autism to immune system

[Chemar]

article in my local paper today

 

Study links autism to immune system

 

Carrie Peyton Dahlberg | The Sacramento Bee

January 27, 2008

 

 

SACRAMENTO, Calif. - In another tantalizing link between the immune system and autism, researchers at the University of California, Davis have found 11 genes, all governing "natural killer" immune cells, that are more active in autistic children than in other youngsters.

 

Though the study is small and preliminary, it bolsters theories that some sort of infectious agent, early in life or even in the womb, might play a role in autism, said Dr. Jeffrey Gregg, director of molecular diagnostics for the UC Davis Medical Center.

 

Read the full article here

http://www.orlandosentinel.com/services/ne...0,4841902.story

[kim]

Cheri,

 

I believe Dr. Sharp, the neurologist who has a daughter affected with TS was involved in that study. He is the one that we discussed on another thread where he said that the results suggested viral involvement in a subgroup.

 

http://www.ncbi.nlm.nih.gov/pubmed/1750347...Pubmed_RVDocSum

 

A subgroup of Tourette's patients overexpress specific natural killer cell genes in blood: a preliminary report.

 

In this proof-of-principle study, we applied Principal Components Analysis to a previously collected set of 16 familial TS and 16 control blood samples to identify subgroups. Fourteen genes, primarily Natural Killer Cell (NK) genes, discriminated between TS and all controls. Granzyme B and NKG7 were confirmed using RT-PCR. Five probesets (four genes) reside in chromosomal regions previously linked to familial TS or obsessive-compulsive disorder. Using the 14 genes, a Principal Components Analysis as well as a cluster analysis identified a TS subgroup (n = 10/16) that overexpressed the NK genes.

 

These are the types of studies that parents need to copy and take to the Dr.s that say that a recent bout of Epstein Barr couldn't possibly have anything to do with an onset of neuro symptoms! Or how about a shot of mercury or aluminum in one arm and a combo MMR+varicella (4 live viruses) in the other. Just maybe it could be a trigger?????

 

http://en.wikipedia.org/wiki/Natural_killer_cell

 

Natural killer cells (or NK cells) are a type of cytotoxic lymphocyte that constitute a major component of the innate immune system. NK cells play a major role in the rejection of tumors and cells infected by viruses. The cells kill by releasing small cytoplasmic granules of proteins called perforin and granzyme that cause the target cell to die by apoptosis.

[kim]

This was the article that mentions Dr. Sharp. I remembered he said in a lecture that's posted here, that the profile seen in a group of TS patients turned out to be very similar to the results of a study involving autistic patients

 

* * * * * * *

 

"What we are seeing can reflect something in the environment that is

triggering the activation of these genes or something genetic that the

children have from the time they were conceived," Sharp explained.

"Such an immune response could be caused by exposure to a virus,

another infectious agent or even a toxin. Another possibility is that

these changes represent a genetic susceptibility factor that

predisposes children to autism when they are exposed to some

environmental factor."

 

From the Desk of Rick Rollens:

 

Gene _Expression Profile Distinctions In Autistic Children Identified

Genomic analysis could add biological certainty to behavioral diagnosis

 

A group of genes with known links to natural-killer cells -- the

first to attack viruses, bacteria and malignancies -- are expressed at

high levels in the blood of children with autism when compared to

children without the disorder, according to a new study from the UC

Davis M.I.N.D. Institute. Researchers also found gene _expression

distinctions in children with early onset and regressive forms of the

disorder. The outcomes, published in the January issue of Genomics,

offer hope that gene _expression analyses can provide biological

evidence of autism, currently diagnosed only through behavioral

assessments, in some children.

 

"What we found were 11 specific genes with _expression levels

that were significantly higher in the blood of children with autism

when compared to the blood of typically developing children," said

Frank Sharp, senior author of the study and professor of neurology

with the M.I.N.D. Institute.

 

"Those 11 genes are all known to be expressed by natural-killer

cells, which are cells in the immune system necessary for mounting a

defense against infected cells. We were surprised by our results

because we were not looking for these particular genes. And while a

number of studies have shown immune system dysregulation to be an

important factor in autism, ours is one of the first to implicate

these particular cells."

 

In conducting the study, Sharp, molecular pathologist Jeff Gregg

and their M.I.N.D. Institute colleagues used blood samples from 35

children diagnosed with autism, 14 with development delay but not

autism and 12 typically developing children. The samples were

subjected to gene _expression analysis using microarrays and compared

for common patterns. In addition to finding the 11 genes with

natural-killer cell connections shared by all of the children with

autism, they identified a pattern of 140 genes differentially

expressed in children with the early onset form of the disorder and a

pattern of 20 genes differentially expressed in children with the

regressive form of the disorder. The team is the first to use genomic

profiling of blood to observe differences in children with autism.

 

A serious and increasingly prevalent neurodevelopmental

disorder, autism is characterized by language impairments, social

deficits and limited, repetitive behaviors. While some parents report

they knew something was wrong with their child close to birth, others

report their children progressed just like others and then lost social

and/or language skills later, usually between the ages of 1 and 2.

 

These separate experiences led clinicians to hypothesize that

there are at least two types of autism -- early onset and regressive.

This study offers biological evidence of those two subtypes.

 

Microarrays are used to examine the _expression levels of

thousands of genes simultaneously. Because of its accuracy, the

technology may become an important diagnostic tool for a variety of

neurological conditions, including ischemic stroke and multiple

sclerosis. To perform the analysis, RNA is isolated from cells in the

blood. Complimentary strands of DNA (cDNA) are then created using the

RNA as a template. Fluorescently labeled cRNA is next made from the

cDNA and hybridized with the DNA on the array.

 

Scanners using laser technology then read the array, revealing

which genes are expressed and at what levels.

 

In addition to being expressed by natural-killer cells, some of

the 11 genes found to be expressed at higher levels in children with

autism are also expressed by CD8+ T lymphocytes -- cells that target

infected cells and, once bound to them, destroy them. It is not yet

clear whether autism involves a primary problem in natural-killer

cells, CD8+ lymphocytes or both.

 

"What we are seeing can reflect something in the environment

that is triggering the activation of these genes or something genetic

that the children have from the time they were conceived," Sharp

explained. "Such an immune response could be caused by exposure to a

virus, another infectious agent or even a toxin. Another possibility

is that these changes represent a genetic susceptibility factor that

predisposes children to autism when they are exposed to some

environmental factor."

 

He added that the current study also does not identify whether

or not the natural-killer cells are functioning abnormally, which

further work by M.I.N.D. Institute immunologists will reveal.

 

"If the natural-killer cells are dysfunctional, this might mean

that they cannot rid a pregnant mother, fetus or newborn of an

infection, which could contribute to autism."

 

Gregg and Sharp consider the findings preliminary until they can

be replicated, but still believe the study results point them in a new

research direction that will shed light on the biological foundations

of autism and eventually lead to new therapeutic targets.

 

The study, "Gene _Expression Profiles in Children with Autism,"

was funded by the National Institutes of Environmental Health Sciences

and the U.S. Environmental Protection Agency through the UC Davis

Center for Children's Environmental Health and the UC Davis M.I.N.D.

Institute. A copy can be downloaded at www.sciencedirect. com.