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Newborn blood may reveal early immune signs of autism

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Alla Katsnelson
22 October 2012

Blood spots: Samples taken at birth suggest that the immune system is dampened overall in children later diagnosed with autism.

Children diagnosed with autism tend to have low blood levels of several immune molecules at birth, according to an epidemiological study published in August in the Journal of Immunology1.

Studies have found differences in the immunological profiles of children and adults with autism, as well as in the mothers of children with autism during pregnancy, but only a handful of studies have examined this issue in newborns.

“There’s something altered about the immune status of these offspring that’s different from [that of typical] children,” says Paul Patterson, professor of biology at the California Institute of Technology, who was not involved in the study.

Similar changes, when observed in children and adults with autism, could be attributed to differences in experiences or stress levels, he says. “What’s important about the newborns is they don’t have any life experience yet.” 

The researchers measured levels of cell signaling molecules called cytokines in dried blood samples taken at birth from 359 people later diagnosed with autism and 741 controls. The samples are from heel pricks conducted during routine newborn screening in Denmark between 1982 and 2000.

“The advantage of using the Scandinavian system, where you have everything registered in a central biobank, is that these samples are collected routinely,” says lead investigator Morsi Abdallah, a researcher at Statens Serum Institute and Aarhus University-Health in Denmark.

The researchers measured the levels of 16 cytokines in the samples and found that 9 of them are at about half the levels in children later diagnosed with autism compared with controls. The children with autism tended to have lower levels at birth of both T helper 1 (Th-1) cytokines, which promote inflammation, and Th-2 cytokines, which quell it.

The results together suggest that the immune system in these children is dampened overall, says Abdallah. The study is the first to suggest that, early in life, children with the disorder have “a hypoimmune pattern,” he says.

A study by the same group of researchers published in early October hinted at low amounts of three nerve growth factors in neonatal bloodspots from children with autism compared with controls. The finding may point to impairment in the brain’s ability to adapt to new information2.

Up or down:

Patterson and others laud the Danish study’s large sample size, but warn that the findings should be interpreted with caution.

One key caveat, noted in the paper, is that the blood spots were collected at least ten years ago. “[Cytokines] are very small molecules that are susceptible to degradation,” says Carlos Pardo-Villamizar, associate professor of neurology and pathology and Johns Hopkins University in Baltimore, who was not involved in the study.

The researchers attempted to control for the degradation by matching the samples from children with autism with control samples taken the same year.

Pardo-Villamizar says it’s also unclear whether the findings suggest an under-active immune system. “The immune system doesn’t work with units; it works with pathways and interactions between molecules,” he says. “So the fact that some molecules are down doesn’t mean the immune system is down.” Using blood spots as a measure of a baby’s immunological activity also requires validation, he adds.

Another potential for noise in the data is how long after birth a heel prick is done, which can depend on birth complications and labor time, says Judy Van de Water, professor of clinical immunology at the University of California, Davis, who was not involved in the study.

“That’s probably the single biggest factor that changes what the immune profile would look like,” she says. “The minute you hit the pavement when you’re born, your immune system is exposed to things and starts being activated and developing.”

Still another concern is diagnosis. The study relied on diagnostic information in old files. Because Denmark changed its definition of autism after 1993, some individuals in the control sample may have later met the criteria for the disorder.

The association between the disorder and cytokine level is complex and subtle, says Van de Water, who is conducting a similar study on blood spots from newborns in California. “We see a difference [in cytokines] between full autism and those that are just on the spectrum.”

Abdallah’s next study may address this concern. He and his colleagues are planning to examine blood spots from a different Danish cohort of 400 children. In this study, child psychologists will first validate the diagnosis based on clinical information from the children’s medical records.

Epidemiological studies such as this one don’t provide insight into mechanisms that might explain the proposed link between immunological factors and autism — for that, researchers must look to animal models. “This kind of work is really only getting started,” says Van de Water.

References:

1: Abdallah M.W. et al. J. Neuroimmunol. 252, 75-82 (2012) PubMed

2: Abdallah M.W. et al. Acta Psychiatr. Scand. Epub ahead of print (2012) PubMed

3: Garay P.A. et al. Brain Behav. Immun. Epub ahead of print (2012) PubMed

Comments

Name: Parent
22 October 2012 - 5:24PM

Will anyone dare investigate how these immune alterations in babies and young children link in to adverse reactions and regressions (worsening of autism symptoms) following vaccinations that many parents observe.

Name: Emily Singer
22 October 2012 - 5:50PM

Thanks for your comment. However, this study was done on newborns who have not received vaccinations, so the findings are not relevant to that issue.

Name: Another Parent
23 October 2012 - 6:43AM

What was interesting was this comment ...

"The results together suggest that the immune system in these children is dampened overall, says Abdallah. The study is the first to suggest that, early in life, children with the disorder have “a hypoimmune pattern,” he says."

Whilst other studies taken in later life suggest some autism follows an autoimmune or autoinflammatory pathway ? Hyperactive ?

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3174192/

Is this how some ASD pathology progresses or do environmental factors play a role ...which could be many things from chemicals , toxins , viruses , bacteria etc

Name: Amedeo Tumolillo
29 October 2012 - 3:42PM

From lead investigator Morsi Abdallah:

Well, the answer is yes. In studies performed later in life a pro-inflammatory state is mostly reported. And such pro-inflammatory state can be a result of environmental insults (i.e. infections). We reported also this in a another study (increased risk of being admitted to hospital due to infection in the same kids when we followed them retrospectively until an average age of 16 years old) [1]. Certainly, this may be an oversimplification of the actual scenario in autism. For example, while the role of environmental factors in the pathology of autism is evident from the several lines of research present by now. There is still a group which can be referred to as “syndromic cases” where the outcome is determined by genetic background regardless of the environmental insults.

Currently, the most optimistic estimates of identified genetic causes for ASD are at about 30% of the total ASD cases [2]. These causes can be grouped in cytogenetically visible chromosomal abnormalities, copy number variants, and single-gene disorders. However and surprisingly, none of the individual causes accounts for more than 1–2% of ASD cases [3]. Furthermore, a recent large-scale twin study suggested that although genetic factors may play an important role in the etiology of ASD, their magnitude may be lower than the earlier estimates, what emphasizes the importance of environmental factors [4].

As a summary, given the mounting evidence suggesting that both genetic and environmental factors play a major role in the etiology of ASD, we are most likely dealing with a scenario of multifactorial etiopathology with pathogenesis, resembling “Two-Hit Theory” first proposed earlier by Alfred G. Knudson in 1971 for retinoblastoma [5]. The model proposes that a first hit in ASD can be either a genetic susceptibility or environmental insult during the fetal period. This is followed by a second (or multiple) hit(s) during pregnancy or infancy that ultimately lead to ASD. In this model, cytokines can play a direct role in translating environmental insults into hindered neurodevelopmental trajectory or represent a biomarker for genetic susceptibility.

1. Abdallah, M.W., et al. Infections during pregnancy and after birth, and the risk of autism spectrum disorders: A register-based study utilizing a Danish historic birth cohort. Turkish Journal of Psychiatry, 2012. DOI: 10.5080/u6847.
2. Miles, J.H., Autism spectrum disorders-A genetics Review. Genetics in Medicine, 2011. 13(4): p. 278-294.
3. Abrahams, B.S. and D.H. Geschwind, Advances in autism genetics: on the threshold of a new neurobiology. Nat Rev Genet, 2008. 9(5): p. 341-355.
4. Hallmayer, J., et al., Genetic Heritability and Shared Environmental Factors Among Twin Pairs With Autism. Arch Gen Psychiatry, 2011. 68(11): p. 1095-1102.
5. Knudson, A.G., Mutation and Cancer: Statistical Study of Retinoblastoma. Proceedings of the National Academy of Sciences, 1971. 68(4): p. 820-823.

Name: RAJensen
23 October 2012 - 7:48PM

The CDC and the Mayo clinic have published vaccination schedules for pregnant women. Newborns hve been exposed to vaccinations whil in the womb:

http://www.mayoclinic.com/health/vaccines-during-pregnancy/AN01886

Name: Mike
23 October 2012 - 11:27PM

Emily : The fact that these children have measurable abnormalities in their immune systems and that these abnormalities are completely ignored by a medical industry that insists EVERY child must be given EVERY available vaccine is clearly relevant.

Name: Parent
22 October 2012 - 8:44PM

Thanks Emily, but my comment wasn't related to this study, but to future research in this field - in other words how/IF these types of immune alterations potentially predispose a young child to adverse reactions to LATER immune stressors, including vaccines.

Name: Lisa
23 October 2012 - 6:51PM

If we dont understand the immune system of newborns why do we give hep B vaccine at birth.

Name: Mike
23 October 2012 - 11:23PM

Hi Lisa,

HepB is given at birth because its considered more politically correct to inject every newborn with HepB than it is to only inject the ones that are being sent home to high-risk families. If your family doctor is telling you there exists evidence to suggest that babies given HepB vaccine at birth have better overall health, run run run.

Name: Sarah
25 October 2012 - 3:09PM

so now there is proof of an immune difference in our kids. So the next step is to start screening all newborns before assaulting their immune systems with 24+ vaccines. Autism parents were right all along- a sensitive subset of kids does exist. We just lacked proof until now. This cookie cutter approach to vaccinating does not work in fact it is dangerous for kids with immune vulnerablities.

Name: mother
16 November 2012 - 6:39AM

The environment (stess, food, drugs etc.) can switch genes 'on' or 'off' = Epigenetics! I may have a very similar genetic make-up to my Autistic son, but he just has had so many more 'environmental insults' as a baby/toddler/child - numerous vaccines, 2 operations as an infant, numerous courses of antibiotics for tonsolitis, respiratory tract infections etc... plus all the 'rubbish' in the food we eat nowadays and the air we breathe! His immune system simply could not cope - and voila! he started regressing into Autism as a toddler!
If I had only known what I know now, I would have done things a lot differently... I would have protected his immunity and not given him drugs, vaccines, artificial ingredients, chemicals and tried to keep his days stress free as much as possible.
We live and learn.

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