Re: NK cells and gene expression

[Guest guest]

You post some of the greatest articles. I am so glad I joined this group.

Jill

Doris and Steve <sjsmith@...> wrote:

RESEARCH

Gene Expression Profile Distinctions In Autistic Children Identified

Genomic analysis could add biological certainty to behavioral diagnosis

From a M.I.N.D. Institute announcement.

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

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

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 Center for

Children's Environmental Health and the UC M.I.N.D. Institute. A

copy can be downloaded at www.sciencedirect.com

[Guest guest]

I'm trying to wrap my brain around this information in

relation to what Dr. G is helping our kids with. Can

someone give me a very " cliff note " & layman's

explanation about NK cells? We don't want these to be

low, correct, because this means the immune system

cannot fight off infections? Is that anywhere near

correct? :-)

Thanks for any insights!!

--- Jill Boyer <sjillboyer@...> wrote:

> You post some of the greatest articles. I am so glad

> I joined this group.

>

> Jill

>

> Doris and Steve <sjsmith@...>

> wrote:

> RESEARCH

>

> Gene Expression Profile Distinctions In Autistic

> Children Identified

> Genomic analysis could add biological certainty to

> behavioral diagnosis

>

> From a M.I.N.D. Institute announcement.

>

> 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

> 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

> 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 Center for

> Children's Environmental Health and the UC

> M.I.N.D. Institute. A

> copy can be downloaded at www.sciencedirect.com

>

> [Non-text portions of this message have been

> removed]

>

>

>

>

>

>

> ---------------------------------

> Be a better friend, newshound, and know-it-all with

> Mobile. Try it now.

>

> [Non-text portions of this message have been

> removed]

>

>

________________________________________________________________________________\

____

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know-it-all with Mobile. Try it now.

http://mobile./;_ylt=Ahu06i62sR8HDtDypao8Wcj9tAcJ

[Guest guest]

Hey

Right - don't want NK cells too low. There is no

mainstream level that is considered low, though, as

they are not connected to illness. But I think I saw

a paper once that said that NKs need to be 8% or more

to properly continuously suppress latent viruses, and

to suppress yeast, etc. However, low NKs are not

considered an immune deficiency - as in plenty of

people walk around healthy with low NKs. There is no

statistical difference in healthy people w/ low NKs

and CFIDS if multiple studies are done (so far). But

low NKs are associated w/anxiety and OCD. I'm not

totally sure how the statistics work on all that. It

is a proven fact that stress and anxiety can decrease

NKs.

I think the NKs are associated w/cellular immunity

(good cellular immunity keeps yeasts well suppressed,

although low NKs don't necessarily mean significant

yeast infections ... but there is an association. And

I think it's mainly just low grade infections.

I also think NKs put out the down-regulating signals -

the anti-inflammatory cells - that shut the immune

system down after infection has ended. Another

important purpose in , as sometimes there aren't

infections but the immune system is over activated.

That's about all I can think of. My & my youngests

NKs run 2% (pretty low) when we're sick, my ASD sons

has been 15% pretty consistently.

HTH

--- Curtis and Hackler <thehacks@...>

wrote:

> I'm trying to wrap my brain around this information

> in

> relation to what Dr. G is helping our kids with.

> Can

> someone give me a very " cliff note " & layman's

> explanation about NK cells? We don't want these to

> be

> low, correct, because this means the immune system

> cannot fight off infections? Is that anywhere near

> correct? :-)

>

> Thanks for any insights!!

________________________________________________________________________________\

____

Be a better friend, newshound, and

know-it-all with Mobile. Try it now.

http://mobile./;_ylt=Ahu06i62sR8HDtDypao8Wcj9tAcJ

[Guest guest]

Hi-I also read this article on the AutismSpeaks website and I was hoping that

someone would?post it on the nids website.?Thanks Doris for posting and it gives

us all hope that we are that much closer to a cure!

Gayle

Re: NK cells and gene expression

You post some of the greatest articles. I am so glad I joined this group.

Jill

Doris and Steve <sjsmith@...> wrote:

RESEARCH

Gene Expression Profile Distinctions In Autistic Children Identified

Genomic analysis could add biological certainty to behavioral diagnosis

From a M.I.N.D. Institute announcement.

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

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

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 Center for

Children's Environmental Health and the UC M.I.N.D. Institute. A

copy can be downloaded at www.sciencedirect.com