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Autism: A disturbed immune system

Overstressed

Senior Member
Messages
406
Location
Belgium
I've found on Sciencedaily.com a quite interesting article:

"Further Evidence Found of Disturbed Immune System in Autism
ScienceDaily (Apr. 16, 2012) A University of Kansas Medical Center study found significantly lower levels of several cytokines, the immune systems messengers and regulators, in the plasma of children with autism disorder (AD) compared to that of unrelated healthy siblings from other families who had members with autism spectrum disorders (ASD).

The study was published in the April 2012 International Journal of Developmental Neuroscience.

In particular, of the 29 cytokine levels analyzed, the researchers found disturbed levels in five related to the T-helper cell immune system and three involved in hematopoiesis or the production of blood cells possibly affecting antibody production required for normal immune system activity.
The immune system and genetic factors have both been implicated in the biological basis for autism, said Merlin G. Butler, professor of psychiatry at the KU Medical Center. Our study further supports a disturbed immune system in children with classic autism that may be related to genetic factors as cytokine proteins are coded by genes distributed among the human chromosomes.

Furthermore, studies in families with autism have shown the significant contribution of genetics, including deletions and duplications of chromosomes and mutations or variants found in specific genes involved with brain development and function, he said.
The importance of identifying early immunological disturbances that may contribute to autism has implications for identifying risk factors, diagnosis and possibly intervention as cytokines may play a role in the function of the developing brain," he said.
The study was one of the largest of its type so far, analyzing the plasma of 99 children with AD between 5 and 10 years of age and that of 40 age- and gende- matched unrelated healthy siblings without AD under the same clinical assessments, specimen processing and laboratory conditions. The male-to-female ratio closely matches that seen in the ASD population, and there were gender-based differences found in five cytokines.
The study is one of only a few to use nanoparticle technology to examine cytokine patterns from peripheral blood in ASD children that requires very small quantities of plasma for analysis and utilizes standardized kits for cytokine assay.
This methodology should allow for other investigators to test the findings of disturbed cytokines in ASD, Butler pointed out.
Butler said that the direction of this research is toward linking the genes encoding immune-related proteins and cytokines to ASD along with identifying the sequence of the events during critical periods of brain and neurological development. This may possibly allow for early recognition, diagnosis and potential treatment.
Ann Manzardo, assistant professor of psychiatry, was the first author on the study.
The study was partially supported by a grant from the Kansas Center for Autism Research and Training at the Life Span Institute of the University of Kansas and with support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Journal Reference:
A.M. Manzardo, R. Henkhaus, S. Dhillon, M.G. Butler. Plasma cytokine levels in children with autistic disorder and unrelated siblings. International Journal of Developmental Neuroscience, 2012; 30 (2): 121 DOI: 10.1016/j.ijdevneu.2011.12.003"

Best regards,
OS.
 

Waverunner

Senior Member
Messages
1,079
Thanks for posting this. For over thirty years now, we see studies that look at certain immune markers, measure cytokines, hormones etc.. But in the end it all seems to be for nothing. We know that the immune system is dysfunctional in many diseases but what exactly is wrong and what exactly can we do about it? The problem I see is that measuring is easier than finding cures. You have nearly no regulations when doing these kind of studies where you take blood to a lab. Moreover they are a lot cheaper than drug development. Unfortunately there is nobody then who puts these findings into practical solutions. This is why I think that people with autism, CFS etc. have to suffer for many more years to come.
 

Daffodil

Senior Member
Messages
5,875
i have come to believe very strongly that there are unidentified pathogens involved in almost every disease but they exist in such low numbers in the body, that they are almost impossible to find.

if lipkin doesnt find a pathogen for cfs, which, in my opinion, is obviously contagious, then there are huge limitations in next generation sequencing. i agree with waverunner...we are going to have to wait a long time for any real breakthrough in the cause of autism.

its really interestiing to read about the success dr. bradstreet is having with gcmaf and autism...all these years all those poor kids suffering with "brain fog" and not being able to tell us!
 

hixxy

Senior Member
Messages
1,229
Location
Australia
I've said this before on the forums, but I had full remission for 1 1/2 weeks. I didn't just recover -- I felt better than EVER. No need to methylation sups to get my energy back up -- it was just there! All neurological problems vanished as well. Then over night collapse and was back at square one.

I've not been able to successfully repeat this. I agree with you though Daffodil. This disease is about hidden infections -- I don't believe our immune systems are just permanently damaged. Our nervous systems on the other hand can only take so much beating.

Unfortunately since this failed recovery, I've gone on to develop extremely severe MCS (was only mild before) and major neurological problems (damage?). I'm not as hopeful of a repeat performance anymore.

I also don't believe we will find a universal pathogen either.
 

Overstressed

Senior Member
Messages
406
Location
Belgium
I found this interesting because some say Autism and CFS/ME are alike, and in the light of the Norwegian findings and these antibody abnormalities, one might say there's indeed at least a problem with B-cells ?

Is that correct to say ? Please correct me if I'm wrong.

Best regards,
OS.
 

natasa778

Senior Member
Messages
1,774
...

4. Discussion

Data from our study in children with AD would indicate a potentially compromised immune system in relationship to unrelated siblings without AD as a comparison group, particularly with suppression of hematopoiesis by low interleukin and colony stimulating factor levels involved with granulocyte production and differentiation [3 of 13 analyzable cytokines (IL1?, IL6 and GCSF) disturbed when examined by diagnosis (AD versus sibling) involved in hematopoiesis]. Five (EGF2, MIP1?, MIP1?, MCP3, and Fractalkine) of the eight cytokines that were lower in children with AD are classified as chemokines and act as attractants in humoral immune response and antibody production. The discussion of other cytokines (e.g., IL4, IL15 and IL13) involved in proliferation of mast cells, promotion of IgE and eosinophilic response to atopy may be warranted although they were not included due to a subthreshold detection laboratory levels. Subthresholds levels of IL13 were significantly more likely to occur in the AD group compared with unrelated siblings without AD further implying lower cytokine levels in children with AD in our report. Unrelated female siblings showed the highest cytokine levels and males with AD showed the lowest. Previous studies have reported increased plasma levels of several cytokines in children with AD compared to children without AD and from families without ASD although increased frequency of autoimmune disorders in families of autistic individuals ( [Careaga et al., 2010], [Comi et al., 1999] and [Sweeten et al., 2003]) implicating immune dysfunction in autism. Our studies further support a disturbed immune system with reduced cytokine levels in the children with AD compared with unrelated siblings of similar age and gender ratio without AD but from families with known affected members with the diagnosis of ASD.

.....

4.2. Implications

Decreased levels of specific cytokines in AD compared with unrelated siblings could alter cellular activity and growth of inflammatory mediators. Three hematopoietin-related cytokines found to be disturbed in our study were IL1? (proinflammatory; fever, leukocyte adhesion, lymphocyte costimulation), IL6 (stimulate hematopoiesis, acute phase responses) and GCSF (stimulate growth and differentiation of granulocytes) ( [Delves et al., 2011], [Noelle and Nowak, 2010] and [Parmely, 2006]). These cytokines activate cells by binding to high-affinity receptors which induce gene expression by activating latent cytosolic transcription factors. The cytokine receptor families are classified as Type I (hematopoietic), Type II (interferon-like), TNF, Ig superfamily and G protein coupled transmembrane receptors. Several disturbed cytokines are ligands for Type I receptors which may contribute to suppression of bone marrow response and cell proliferation, growth and differentiation which may impact on antibody production and immunity ( [Hankey, 2009], [Hu and Ivashkiv, 2009], [Noelle and Nowak, 2010], [Parmely, 2006] and [Wei et al., 2008]).

Five of the 14 chemokines (EGF, Fractalkine, MCP3, MIP1?, and MIP1?) are small chemoattractant peptides, produced mostly by activated T cells, and establishes a chemical concentration gradient that is sensed by the cell to induce expression of leukocyte integrins that mediate leukocyte binding and migration. Therefore, chemokines can act as an attractant, but also induce cytoskeletal changes that mediate cell migration. In our study, MIP1? and MIP1? (macrophage inflammatory proteins) and Fractalkine found to be decreased attract T lymphocytes, natural killer cells, dendritic cells and monocytes. MCP3 which attracts only monocytes showed reduced levels in our children with AD. Interestingly, EGF (epidermal growth factor) is a growth factor involved with wound healing by attracting fibroblasts and epithelial cells and reduced in the AD group compared with unrelated siblings. Activated immune cells use cytokines, chemokines or growth factors to survive and repopulate. Data from our study would indicate a potentially compromised immune system in AD in relationship to unrelated siblings without AD as a comparison group.


4.3. Summary

Plasma was obtained from the AGRE repository on a relatively large number of well-characterized children with AD and unrelated siblings without autism between the ages of 5 and 10 years from families with members affected with ASD. We used log-transformed cytokine levels with analysis of covariance and a general linear model adjusted for diagnosis, gender, diagnosis by gender interaction effects, age and days of specimen processing. The cytokine status may be different in unrelated siblings compared to children with no family history of ASD, but was not the focus of our study. Two of the seven cytokines (i.e., TNF? and IFN?) analyzed by Saresella and others in 2009 in children with ASD (mean age = 15y) and healthy non-autistic siblings were found to be significantly different (higher in ASD) measured using monoclonal antibodies to identify the cytokine levels. Levels of IFNg and TNF? were not significantly different in our AD group compared with unaffected and unrelated siblings from other AGRE families with ASD. IFN? levels were found to be lower in the males in our study compared with females when grouped together regardless of diagnosis.

The main findings of our study were lower levels of cytokines from the chemokine family which participate in the Th1 immune system and hematopoiesis. Our data further supports impaired hematopoiesis due to reduced growth factors and antibody production contributing to ASD compared to unrelated siblings without AD. ...

link to full paper:
http://www.sciencedirect.com/science/article/pii/S0736574811001912


I agree with Waverunner - however 'interesting' these findings are (it has been known for decades now that the immune system is dysfunctional in autism...) all this research is really a pointless waste of money unless it is translated into treatments very soon...
 

hixxy

Senior Member
Messages
1,229
Location
Australia
Sigh. You also have to remember Natasha, that even once they find the problem and devise a "treatment" or drug for it. If allopathic medicine has their way we'll have to wait through another 10 years worth of clinical trials, then approval, then doctor education ....... How depressing.
 

currer

Senior Member
Messages
1,409
But these immune abnormalities, if prior to the development of AD could explain why some children respond to vaccination by developing AD
 

natasa778

Senior Member
Messages
1,774
But these immune abnormalities, if prior to the development of AD could explain why some children respond to vaccination by developing AD

Absolutely. Imo it also explains why some mildly affected children turn much more severe following vaccinations or infections - adding insult to injury and such.


Another 'interesting' phenomena often observed in some kids with autism is disappearance of many symptoms during fever. You hear parent saying that the higher the fever the more typical their child is, for some those are the only times they are able to hold conversation, interact etc.
 

Waverunner

Senior Member
Messages
1,079
Another 'interesting' phenomena often observed in some kids with autism is disappearance of many symptoms during fever. You hear parent saying that the higher the fever the more typical their child is, for some those are the only times they are able to hold conversation, interact etc.

Just anecdotal but this is true for me, too. Maybe once a year I have fever and during that time my brain fogs clears up and I feel normal. Of course I'm exhausted during that time and lots of other symptoms show up that come along with the fever but my thinking as well as my emotions normalize.
 

hixxy

Senior Member
Messages
1,229
Location
Australia
Bring on the fevers! I haven't had a cold, flu or anything else that might result in a fever for over 4 years now..
 

natasa778

Senior Member
Messages
1,774
Just anecdotal but this is true for me, too. Maybe once a year I have fever and during that time my brain fogs clears up and I feel normal. Of course I'm exhausted during that time and lots of other symptoms show up that come along with the fever but my thinking as well as my emotions normalize.

could this be linked http://www.internationalcancertherapy.com/ewbh.php

or down to fever directly affecting levels of neurotransmitters:

1. The acute hyperthermia induced by exposure to elevated ambient temperatures (40C) during 90 min produced dramatic changes in certain brain transmitter amino acid levels in infant rats.
2. All inhibitor transmitter amino acids, except taurine, rose significantly in 7 and 14 day-old rats. The effect of acute hyperthermia in excitatory transmitter amino acids was opposite, glutamic acid increased and aspartic acid decreased.
3. Taurine, that does not change during acute hyperthermia is the amino acid whose concentration suffers the greatest change with age.
4. The greater rise of body temperature in 21 day-old rats, was associated to slight changes in brain transmitter amino acid levels. These findings suggested that lower rise on body temperature found in 7 and 14 day-old rats may be related to the higher increase of inhibitor transmitter amino acids.
http://www.sciencedirect.com/science/article/pii/0306362382900568


... These novel observations suggest that (i) glutamate, aspartate, GABA and glycine are involved in the pathophysiology of heat stress, and (ii) a balance between excitatory and inhibitory amino acids in brain is crucial in hyperthermia induced brain injuries or repair.

http://www.ncbi.nlm.nih.gov/pubmed/16550328

and http://www.ncbi.nlm.nih.gov/pubmed/17645925