Maternal antibodies involved in aetiology of autism(s)

26 Mar

A new study released by John Hopkins indicates that maternal antibodies may play a role in the aetiology of autism:

[a]…possible explanation involves the transfer of reactive antibodies from the mother through the placenta to the fetus.

To investigate the latter, the team measured the antibody-brain reaction in blood samples from 100 mothers with and 100 mothers without a child diagnosed with autism.

Mothers of children with autism had a stronger reactivity or more areas of reactivity between antibodies and brain proteins compared with mothers without an autistic child. The presence of maternal antibodies also correlated with having a child with developmental regression, a primary feature of autism.

Things to note. No one, repeat no one is assigning _blame_ to mothers. I have no doubt there will be an attempt in some quarters to twist this into an attack on the sainthood of autism parents but its really not. Biology is biology. C’est la vie. Nobody in this study had the last name Bettlehiem.

Its a fascinating hypothesis though. Along with the latest cutting edge science that has found a genetic basis in approximately 40% of autism this hypothesis utilises good ideas in a rigorously scientific way. Of course, it may well turn out to be wildly wrong, but its a nice change to see some science that’s not about cure or vaccines but just interesting in and of itself.

20 Responses to “Maternal antibodies involved in aetiology of autism(s)”

  1. MJ March 27, 2008 at 02:42 #

    Along with the latest cutting edge science that has found a genetic basis in approximately 40% of autism

    No, the article you link to is talking about does not say “has found”. As a matter of fact it says :

    “The three-tiered approach will yield a specific genetic diagnosis in approximately 40 percent of patients with autism-spectrum disorders”

    Notice the use of the work will in the sentence. Don’t count your genetics before they are hatched.

  2. Ms. Clark March 27, 2008 at 03:43 #

    They already DID find 40% of a group that they ran through the step-wise process of eliminating/confirming genetic disorders.

    Been done. A couple years ago. No. Really.

    Srsly and everything. I reported about it
    http://autismdiva.blogspot.com/2006/09/so-many-studies-so-little-time.html
    a year and a half ago and the research was more than 10 months old then! Hmmmmm.

    I don’t know if other centers are using this method of finding all kinds of genetic/congenital probs…. but this might be the new standard. 40% of kids have a genetic or currently known congenital problems like fetal alcohol or CRS or valproate exposure or ??? and 20% have moms who had flu antibodies go wacky and turn into anti-fetal-brain antibodies or something ….

    The rest will turn out to be alien changelings, of course. :-/

  3. Kev March 27, 2008 at 06:54 #

    MJ, the science – as Ms Clark notes – is done already. They’re just approximating what percentage will be accounted for. As I understand it, 40% is a conservative estimate.

  4. Maya M March 27, 2008 at 07:01 #

    I have my doubts, however. As far as I know, epidemiological studies haven’t revealed preferential “inheritance” of autism from the mother, as should be expected. And antibodies against natural tissue components are more likely to reflect tissue destruction than to cause it. E.g. after a myocardial infarction, there are (auto)antibodies against heart antigens but they haven’t caused the infarction.

  5. Ms. Clark March 27, 2008 at 10:23 #

    What they are saying, as I read it, is that the moms don’t exactly have “auto” anttibodies, they have antibodies that react with fetal brain tissue….

    and here’s the kicker. The mom doesn’t have to have been pregnant before one time in order for these antibodies to have affected the first kid, so they are guessing that she’s been exposed to something, like maybe the flu, and those antibodies are misguiding themselves to attack fetal brain tissue. I have no idea if that’s the case, but that’s the idea…. so I understand it. You might be able to inquire of the scientists.

    I don’t know if they find these antibodies in women with no kids, but I would suspect that they would, so long as the woman had been exposed to whatever it is that’s making these antibodies.

  6. Lenora March 27, 2008 at 13:58 #

    Schaefer (the lead researcher in the 40% report you talked about) just wrote another piece with Nancy Mendelsohn in Genetics in Medicine re-iterating the need for a tiered approach to genetic testing and autism. This time he includes the pten gene mutation as a factor in autism and macrocephaly. I’m interested in that because I have two ASD kids with really big heads. When I search the literature, however, I can only find about a dozen kids who are actually identified with autism and the pten gene mutation. I don’t know if the research is that new or the mutation is that rare. I wrote to Schaefer asking if getting a genetic screening for the pten mutation is a realistic avenue to pursue yet. I’ll be interested to hear his reply.

  7. alyric March 27, 2008 at 14:04 #

    I’m having a spot of bother with this ‘stronger reaction’ conclusion since it’s pretty inconclusive. It’s not a flat negative is it? Seems like it’s perfectly normal to have these sorts of antibodies since mothers of apparently normal kids have them, albeit not so strongly. It would be interesting to read the paper especially the bit about the specificity of the testing.

  8. Catherina March 27, 2008 at 14:29 #

    alyric – you can email me at

    catherina at mail2world dot com

    for the pdf, if you want.

    Kev – it’s Johns Hopkins

  9. Kev March 27, 2008 at 15:50 #

    Yeah but me n John are mates so we get a bit informal sometimes 😉

  10. passionlessDrone March 27, 2008 at 16:34 #

    Hello friends –

    I’m not sure we should put much weight into a 40% range based on the study referenced by Ms. Clark. This sample was based on a population of people referred to a clinic for genetic testing. Isn’t this a considerable source of bias if we are to try to draw conclusions about the population as a whole? I’m not saying genetics isn’t at play, but I am saying that study doesn’t come anywhere close to proving it is 40%.

    Along the lines of the OP, some might be interested in knowing that in animal models, ‘autism like behaviors’ have been created by injecting animals with a dose of IL-6; a cytokine produced during infection.

    http://www.physorg.com/news110641743.html

    The team tried injecting the pregnant mice with individual cytokines, rather than with poly(I:C). It turned out that after a single dose of a specific cytokine known as interleukin-6 (or IL-6), a mouse would give birth to offspring who, at maturity, exhibited the familiar schizophrenia- and autism-like behaviors.

    To confirm the role of IL-6, Steve Smith, the lead researcher, gave fake colds (poly(I:C)) to two groups of pregnant, IL-6-free mice. One group had received anti-IL-6 antibodies which blocked IL-6; the other consisted of so-called IL-6 knockout mice (mice whose genetic makeup prevents them from synthesizing IL-6). In both groups, offspring grew up normal, showing that IL-6 is necessary for the maternal poly(I:C) treatment to alter fetal brain development and subsequent behavior in the offspring.

    The decision to try injecting IL-6 was a long shot. “It is really unexpected that a single injection of a single cytokine would exert such a powerful effect,” says Patterson.

    To insure I get flamed enough, I thought it appropriate to point out that getting a flu vaccination is a surefire way to produce huge jumps in IL-6.

    http://www.ncbi.nlm.nih.gov/pubmed/15976761?ordinalpos=7&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

    “Plasma CRP, interleukin (IL)-6, monocyte chemotactic protein 1, tumor necrosis factor alpha, IL-2 soluble receptor alpha, and serum amyloid A were measured, and differences in mean concentrations of absolute and normalized values on days 1, 3, and 7 were compared with mean baseline values. There was a significant increase in mean IL-6 (P ”

    The CDC currently recommends all pregnant women receive the flu vaccine.

    http://www.cdc.gov/flu/protect/keyfacts.htm

    The article was quite interesting. Thanks.

    Take care all!

    – pD

  11. Leila March 27, 2008 at 17:48 #

    Hi Kev. I find all the causation research fascinating but I’m not really emotionally invested on it. My son is autistic, at this point it won’t matter much “how” he became this way; my most pressing concern is understanding his type of intelligence better so I can help him develop to his full potential. On a weekly basis I come up with some theories and strategies for his education… I wonder if there are already some studies on autistic intelligence and education that can help me compare and analyze my own findings and choose the best methods, beyond the ABA/Floortime basics that are very limited in my opinion.

    So, my point is, I’d love to see you talk a little bit about cutting edge research on autism education.

    Thank you.

  12. notmercury March 27, 2008 at 19:52 #

    Hi passionlessDrone ,
    There are a few other maternal antibody studies that found similar numbers, though different antibodies.

    Regarding IL-6, true the flu vaccine can induce IL-6 elevations but nothing compared to the levels or duration from the actual infection.

    If the vaccine were to increase the risk of having an autistic child, I would think it would have to be given during a relatively narrow window of opportunity.

  13. Joseph March 27, 2008 at 20:03 #

    So, my point is, I’d love to see you talk a little bit about cutting edge research on autism education.

    I wish there were a lot more on that than, you know, “point to blue” and “cat or dog?”

    You might be interested in this paper by Dawson, Mottron & Gernsbacher.

  14. Ms. Clark March 27, 2008 at 20:04 #

    The women whose antibodies were used in the study the MIND did, had children who are autistic for their first pregnancies. The antibodies were there in the mom apparently, when she got pregnant. This is not about IL-6. This is not about moms getting the flu when they were pregnant even. The point is that if they have the antibodies before they get pregnant, those antibodies might rearrange their kids’ neurons. This is what they are showing or trying to show with injecting these very same antibodies into mice and monkeys.

    The way to prevent this would be to prevent women from forming flu antibodies, maybe. Sure doesn’t seem too likely. They’d have to put all female babies into glass bubbles keep them there until they grow up and when they want to have babies they could get artificially inseminated (can’t have contact with some guy who might have the flu) and then they’d have to stay in those glass bubbles until they decide they don’t want any more kids….

    Hmmm. I say embrace the autistic kids and forget trying to freak out the moms, or trying to terrorize them away from flu vaccines.

  15. Leila March 27, 2008 at 21:30 #

    Thanks for the link, Joseph. I wish Dawson, Mottron and Gernsbacher could see my kid – I’d be interested in contributing to their studies.

  16. Kev March 27, 2008 at 21:32 #

    Leila, you’re absolutely right and I have discussed these things before but the topic of education varies so wildly from country to country that I think it would be of limited interest.

  17. Kev March 27, 2008 at 23:31 #

    Regarding EN2 mutation:

    Millonig and Brzustowicz had previously demonstrated an association with the gene in a sample of 167 families with autism. The new study adds another 351 families and now provides convincing statistical support for the existence of a mutated form of EN2 that increases the risk for autism. The statistics also showed EN2 may contribute to up to 40 percent of autism cases in the general population.

  18. María Luján March 28, 2008 at 01:17 #

    Hi
    There are two recent manuscripts related
    Brain Behav Immun. 2008 Feb 7 [Epub ahead of print] Links
    Stereotypies and hyperactivity in rhesus monkeys exposed to IgG from mothers of children with autism.Martin LA, Ashwood P, Braunschweig D, Cabanlit M, Van de Water J, Amaral DG.

    Autism together with Asperger syndrome and pervasive developmental disorder not otherwise specified form a spectrum of conditions (autism spectrum disorders or ASD) that is characterized by disturbances in social behavior, impaired communication and the presence of stereotyped behaviors or circumscribed interests. Recent estimates indicate a prevalence of ASD of 1 per 150 (Kuehn, 2007). The cause(s) of most cases of ASD are unknown but there is an emerging consensus that ASD have multiple etiologies. One proposed cause of ASD is exposure of the fetal brain to maternal autoantibodies during pregnancy [Dalton, P., Deacon, R., Blamire, A., Pike, M., McKinlay, I., Stein, J., Styles, P., Vincent, A., 2003. Maternal neuronal antibodies associated with autism and a language disorder. Ann. Neurol. 53, 533-537]. To provide evidence for this hypothesis, four rhesus monkeys were exposed prenatally to human IgG collected from mothers of multiple children diagnosed with ASD. Four control rhesus monkeys were exposed to human IgG collected from mothers of multiple typically developing children. Five additional monkeys were untreated controls. Monkeys were observed in a variety of behavioral paradigms involving unique social situations. Behaviors were scored by trained observers and overall activity was monitored with actimeters. Rhesus monkeys gestationally exposed to IgG class antibodies from mothers of children with ASD consistently demonstrated increased whole-body stereotypies across multiple testing paradigms. These monkeys were also hyperactive compared to controls. Treatment with IgG purified from mothers of typically developing children did not induce stereotypical or hyperactive behaviors. These findings support the potential for an autoimmune etiology in a subgroup of patients with neurodevelopmental disorders. This research raises the prospect of prenatal evaluation for neurodevelopmental risk factors and the potential for preventative therapeutics.
    Neurotoxicology. 2008 Mar;29(2):226-231. Epub 2007 Nov 6. Links
    Autism: Maternally derived antibodies specific for fetal brain proteins.Braunschweig D, Ashwood P, Krakowiak P, Hertz-Picciotto I, Hansen R, Croen LA, Pessah IN, Van de Water J.

    Autism is a profound disorder of neurodevelopment with poorly understood biological origins. A potential role for maternal autoantibodies in the etiology of some cases of autism has been proposed in previous studies. To investigate this hypothesis, maternal plasma antibodies against human fetal and adult brain proteins were analyzed by western blot in 61 mothers of children with autistic disorder and 102 controls matched for maternal age and birth year (62 mothers of typically developing children (TD) and 40 mothers of children with non-ASD developmental delays (DD)). We observed reactivity to two protein bands at approximately 73 and 37kDa in plasma from 7 of 61 (11.5%) mothers of children with autism (AU) against fetal but not adult brain, which was not noted in either control group (TD; 0/62 p=0.0061 and DD; 0/40 p=0.0401). Further, the presence of reactivity to these two bands was associated with parent report of behavioral regression in AU children when compared to the TD (p=0.0019) and DD (0.0089) groups. Individual reactivity to the 37kDa band was observed significantly more often in the AU population compared with TD (p=0.0086) and DD (p=0.002) mothers, yielding a 5.69-fold odds ratio (95% confidence interval 2.09-15.51) associated with this band. The presence of these antibodies in the plasma of some mothers of children with autism, as well as the differential findings between mothers of children with early onset and regressive autism may suggest an association between the transfer of IgG autoantibodies during early neurodevelopment and the risk of developing of autism in some children.

  19. mayfly March 28, 2008 at 02:44 #

    The article states there are mothers of typical children which show similar reactivity. It warns that such sensitivity therefore is not deterministic, and goes on to say the relationship is complex not direct.

  20. Ms. Clark March 28, 2008 at 04:25 #

    Thank goodness, Mayfly, because Amaral is already positing a treatment. Get a “clean” surrogate mother who doesn’t have these antibodies or put mom’s blood through a scrubber while she’s pregnant (a few times?), aka plasmapheresis. In the hopes of her not having an autistic kid … and I guess in the hopes that doing the plasmapheresis doesn’t cause some other more awful disorder, from the mom’s point of view.

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