Maternal Immune Systems and Maternal Antibodies: A causal factor for some cases of autism?
Researchers at the University of California-Davis M.I.N.D. Institute suggest that some cases of “regressive autism”—-in which a child seems to be developing normally and then loses skills and becomes autistic, in contrast to “early onset autism”—-may be connected to the immune systems of mothers during pregnancy. Antibodies in the blood of mothers of autistic children were found to bind with fetal brain cells and affect healthy brain development. More specifics about the study from Science Daily:
[Judy] Van de Water, senior author of the study and professor of rheumatology, allergy and clinical immunology, and her team began their research with blood samples from 123 mothers – 61 whose children have autism and 62 whose children are typically developing. They isolated IgG antibodies from the samples then exposed the antibody to fetal brain tissue by western blot analysis, which detects antibody reactivity to proteins. The outcome revealed a highly specific reactivity pattern to two fetal brain proteins in seven of the 61 samples from the autism group, six of which were from mothers of children who had regressive autism. None of the IgG samples from mothers in the control group produced this same result.
“We’re not entirely sure why the IgG response against fetal brain proteins was so specific for later onset autism,” said Van de Water. “It’s possible that early exposure to maternal antibodies sets in motion a biological path to autism with the behavioral outcomes not apparent until much later. It’s also possible that an environmental exposure sometime after birth could be required to set this process in motion. We are hopeful that this study will help build our understanding of the foundations of the regressive form of the disorder.”
……..
IgG antibodies are responsible for long-term immune system responses to infection, but they can also contribute to autoimmune diseases such as arthritis, multiple sclerosis and lupus. IgG also crosses the placenta in order to provide key immune system protectants to a growing fetus and newborn child, which is a key reason why Van de Water decided to investigate the role of IgG as a potential factor in autism.
Van de Water next wants to know if IgG in women during the time of their pregnancies produces the same response to fetal brain proteins. Women in the current study were two-to-five years beyond childbirth. She will now conduct the same study with women who are pregnant and already have a child with autism, because such women are much more likely to have another child with the disorder.
“If women in this next phase of the study give birth to a child eventually diagnosed with autism, blood analyses from all stages of her pregnancy will give us a clear picture of the immune system factors that were in play during gestation and could have altered her child’s neurodevelopment,” Van de Water said.
Researchers are hopeful that a prenatal test and therapeutic interventions preventing IgG exposure during pregnancy could “protect some children from ever getting autism.” This is the first study to consider the immune systems of mothers of autistic children; a growing number of studies has investigated autistic children’s immune systems. The findings will be published in the March 2008 issue of Neurotoxicology.
Another study conducted by researchers from the M.I.N.D. Institute builds on Van de Water’s research and shows that an interaction between fetal brain cells and antibodies in mothers’ blood could be linked to “stereotypies” such as flapping, toe-walking, spinning, and other repetitive behaviors often noted in autistic children. The study will be published in a future issue of Brain, Behavior, and Immunity. From Science Daily:
[Neuroscientist David] Amaral and his research team at the California National Primate Research Center exposed eight rhesus monkeys to human IgG at three times during the end of the first trimester of pregnancy. Four monkeys received IgG from mothers of children with autism, while four received antibody isolated from the blood of mothers of typically developing children to ensure that any potential outcomes were not due to human IgG exposure. Five monkeys received no treatment whatsoever and were included as study controls. The behavior and social interactions of all 13 offspring were then carefully observed and recorded over the course of a year-and-a-half in a variety of familiar and novel settings.
The team identified only mild social alterations in the four monkeys treated with IgG from mothers of children with autism. The monkeys’ behavior, however, was notably distinct, since all of them exhibited repetitive activities such as pacing, backflipping, twirling and swinging with much greater frequency and for longer periods of time than other monkeys in the study. The stereotypies were most pronounced after weaning and were even more striking in unfamiliar settings.
“The major significance of this study is that it links exposure to abnormal immune system factors during pregnancy with specific behavioral outcomes in offpsring,” said Amaral. “The monkeys’ behavior is profoundly changed from normal, and those changes are similar to impairments that we see in children with autism. The study adds to increasing evidence that immune system factors of mothers could contribute to the development of some forms of autism.”
While the finding is remarkable, the results must be replicated in a larger, more comprehensive study before prenatal IgG exposure can be confirmed as a risk factor for autism. At that point, the researchers are hopeful that clinical protocols can be developed to identify this risk factor during pregnancy.
Such “stereotypies” are only one feature of autism, though they are “part of one major symptom category — in addition to social deficits and language impairments — of the autism diagnosis”; clinicians do not know why autistic persons engage in these behaviors. My own observations of my son Charlie—he does not flap or toe walk, but paces, among other things—are that he performs these behaviors to comfort, calm, and soothe himself; more than a few autistic adults have noted the same.
Researchers note that the study is small and that its results need to be replicated to further investigate if a causal factor for some cases of autism has been discovered. Loren Martin, the lead author of the study and now a professor of psychology at Asuza Pacific University, notes that these findings are still at an “early stage” of being investigated. Treatments like those for used for autoimmune and inflammatory diseases”—such as lupus, arthritis, and multiple sclerosis—-might be developed.
Tags: asd, asperger, autism, autism spectrum disorder, children, davis, immune system, lupus, MIND Institute, MS, pdd-nos, primates, PsychologyRelated Stories
POSTED IN: Baby, Cause, Health, Parenting, Sensory, Treatment
26 opinions for Maternal Immune Systems and Maternal Antibodies: A causal factor for some cases of autism?
Translating Autism
Feb 12, 2008 at 10:48 am
Wow Kritisna, this is fascinating research. It is still in line with the functional migration theory of regressive autism, since it provides a possible explanation for what could be leading to the disruption of the migration process during the key early months of life. I just printed Amaral’s article and will review it tomorrow. Thanks, Nestor.
Nestor Lopez-Duran PhD
Translating Autism
Bad Mommy
Feb 12, 2008 at 11:48 am
I have always thought that very small differences in the way that the fetus interacts with the mother, or very small differences in eggs or sperm that have been on the shelf for longer, might be at work in some of the forms of autism. The prevalence in males born after an initial male, and the increased risk down a line of male offspring, suggest that there may be an immune component. What is now recognized in the maternal immune response role in the risk of developing schizophrenia is also interesting in this regard.
I’m glad that scientists are finally starting to treat “autism” as a similar group of symptoms for what may turn out to be a very broad group of different disorders.
Lisa/Jedi
Feb 12, 2008 at 12:31 pm
Hmmm… I just wish that there were bette diagnostic criteria for “regressive autism”. I wasn’t aware that it has been demonstrated to be a clear subset of autism, since it’s something that depends on parents’ observation, rather than something with clear diagnostic boundaries. It makes me nervous that they are researching & forming opinions of something that is still not clearly understood. Having a lab research background, I worry that throwing the not well understood “regressive” autism into the mix may be highlighting something that isn’t “really” there. Yes, it’s possible that this may point to “regressive” autism as an actual subgroup, but they’ll need to be awfully careful of how they look at the data (& how they’re defining “regressive” autism) before they’ll get anything of practical use from their results. I agree that the study size needs to be bigger before any conclusions may be drawn… not that that this will stop them from drawing whatever conclusions they want to (remembering the “tv causes autism” brouhaha…).
Chuck
Feb 12, 2008 at 1:13 pm
“Regressive autism”, “High Functioning Autism”, “Low Functioning Autism”. They are all the same. There is no diagnostic criteria for any of them any yet “professionals” throw them around like they know what they are talking about and these terms mean something.
Dave
Feb 12, 2008 at 6:19 pm
Pretty ignorant statement Chuck- Even though there is no diagnostic criteria, to say it is all the same is pretty narrow minded. My son is high functioning- others I have seen and heard about through support groups are not. I shouldn’t need to spell out the differences…
stopautismquackery
Feb 12, 2008 at 6:34 pm
To classify a human being’s very core on a supposed ‘functioning scale’? I wonder just who is being narrow-minded?
Regan
Feb 12, 2008 at 6:40 pm
How about rather than declaring it defacto regressive “autism” to specify it in terms of what it does say, that in this experiment that prenatal maternal IgG exposure to the fetus demonstrated post-natal stereotypy development not present at birth?
Time and further research will tell whether this is a true relationship to some of the motor differences seen in human autistic spectrum disorder/pervasive developmental disorder. The researchers themselves characterize the study as preliminary.
To my mind, “autism” is an observational definition of a constellation of diagnostic criteria of which not all have to be met to receive the diagnosis; the root causes could be multiple and varied, with different degrees of severity. I think of it more as “an autism”. I doubt if all cases are going to be the same thing or the same cause.
xtiluv
Feb 12, 2008 at 7:10 pm
Kai and I are participating in a MIND Institute study and plan to continue with others if they seem safe and applicable to our situation. The CHARGE study that we are currently involved in is looking for genetic and environmental causes for autism. There isn’t a lot of value to us on a personal level, but I feel we are doing something to add to the conversation.
I suspect that the answer (if they find one) will not be crystal clear and that a plethora of variables come into play. I also think that the blanket term of autism will be further refined by doing this type of research, allowing us to begin to target the needs of individuals more appropriately.
It is exciting to feel that we are able to be a part of something bigger than ourselves and I really hope that the outcome is something that can help others in the future. Sometimes it seems as if it might add a bit more meaning to our daily grind. At least, that’s what I tell myself.
Translating Autism
Feb 12, 2008 at 7:13 pm
What really saddens me about this entire issue is the belief by some people that researchers have a particular agenda to conspire against people with autism and their families. This is sad because most of these researchers have spent their lives trying to contribute to our understanding of Autism for the benefit of people with autism and their families.
Categorizations exist only to the extent that they have, or have the potential to provide, some utility in regards to our understanding of the causes, and the creation of treatment interventions. If the classification of high vs low functioning autism, or regressive vs typical autism, leads us to more clearly identify possible causes, or possible profiles that respond better to one treatment intervention over another, then such classification served its purpose. If we soon find that such categorization provides absolutely no utility, then it will be dropped in preference to some unitary construct. But the presentation of autism is so diverse, that it is likely that one day we will learn that we were actually looking at 3-4 completely different conditions that just happen to have similar symptoms.
Nestor L. Lopez-Duran PhD
Translating Autism
stopautismquackery
Feb 12, 2008 at 7:43 pm
“If the classification of high vs low functioning autism […] then such classification served its purpose.”
At the cost of making a person feel lessor?
At the peril of being less valued in our society?
stopautismquackery
Feb 12, 2008 at 7:48 pm
“lesser”
(*ahem* fixated on ‘Flip This House’)
xtiluv
Feb 12, 2008 at 8:45 pm
@Translating Autism-
Well said. You have beautifully expressed what I have thought many a time.
@stopautismquackery
I do think we have to be careful with our language, but since we are still developing the appropriate ways to speak about these things, we are going to make some mistakes along the way. I think we really have to look at the intent of the language, more than the words themselves.
I try very hard to find diplomatic ways to phrase my thoughts, but I find that sometimes I fail. Maybe we should try to improve on these labels. Try to find new, better ways to express the ability levels than high and low.
I don’t think anyone means to devalue others with this language, although I understand that can be the effect.
stopautismquackery
Feb 12, 2008 at 9:05 pm
“Higher than Mountains or Lower than Valleys?”
http://thiswayoflife.org/blog/?p=271
Kristina Chew, PhD
Feb 12, 2008 at 9:23 pm
I do think our language for talking about “all this” is limited—-while I question what is meant by terms like “high-functioning” and “low-functioning,” sometimes they seem the only (or the fastest) way to explain about Charlie—-soon as the words come out of my mouth, I find myself questioning what I just said at times.
@xtiluv,
“adding to the conversation”—yes, much for everyone to add and keep adding—–
Translating Autism
Feb 12, 2008 at 9:47 pm
Kristina, your comment made me think that part of this controversy is less about categorization and more about semantics. I agree the terms “low functioning” and “high functioning” are unfortunate choices, as they may be interpreted as statements or judgments of “value” even though, as you mentioned, most often they are simply descriptors of the severity of specific symptoms (language for example). I wish they had different names. When I talk about categorization I was actually thinking more about diagnostic categorization, or the general perspective that the more we can narrow our identification of a particular syndrome and differentiate it from others, the more likely we are to develop more effective treatment interventions and understand its causes. There must be a way for this to happen without devaluing the worth of children or adults with autism, and maybe changing our semantics is a step, albeit small. Nestor
Nestor Lopez-Duran PhD
Translating Autism
Regan
Feb 12, 2008 at 10:51 pm
Dr. Lopez-Duran,
The problem is the lack of specific definition and context for those kind of labels.
My daughter was categorized as “high”, “low” and “medium” functioning within the course of a year and not necessarily in the order one expects.
So my point of view is not only can those be subjective, but broad labels may imply global abilities/inabilities not representative of specific true abilities. I think it is more helpful to identify specifics than use shortcuts subject to misunderstanding.
Michelle Dawson
Feb 12, 2008 at 11:04 pm
In reponse to Dr Lopez-Duran, in autism research, “high” and “low functioning” are terms of convenience which refer to snapshot measurements of intelligence or developmental level. This is their only legitimate use. They do not, as Dr Lopez-Duran claims, describe autism “severity. Autism “severity” is the attempt to quantify the extent to which autistic traits and abilities (what Dr Lopez-Duran calls “symptoms”) are obvious.
Very occasionally, researchers get it wrong (I know of a few examples), but if you have read the research, you will know that “high” and “low-functioning” refer to snapshot intelligence (or developmental) levels as measured by specific instruments, not to autism “severity.”
We presented data last year at IMFAR showing that “severe” autism phenotypes were not associated with low intelligence. That is, “severity” was not associated with level of functioning (as in, “high” or “low functioning”).
And “high” and “low functioning” do not describe kinds of autistics. They describe ranges of scores on tests of intelligence (or developmental level).
Autistics who fall in the “low functioning” range on one instrument or at one time may fall into the “high functioning” range on another instrument or at a different time. Autistics’ intelligence (that is, our level of functioning) seems to be much more variable across time and instruments than in nonautistic populations.
Also, autistics in the “low functioning” range have performed better on some tasks than typical children matched on age (that is, of much higher measured intelligence or developmental level).
I don’t think the problem is “semantics.” The problem is accuracy. Accurate information is always good for autistics. Claiming that “high” and “low functioning” “most often are simply discriptors of the severity of specific symptoms” is simply false. So are many other unfounded assumptions about “high” and “low functioning.”
Dave
Feb 12, 2008 at 11:05 pm
“To classify a human being’s very core…”
If you thought I was questioning my sons core with describing his condition you are flat wrong and I take offense even to the notion. We are talking about a descriptive way to describe his condition- to read into anything more really makes wonder who the “quack” really is…
Translating Autism
Feb 13, 2008 at 12:20 am
re: Michelle Dawson
I stand corrected. Clearly I used the wrong analogy and description to refer to differences in high vs low functioning autism. And the the accuracy and distinction you correctly describe speaks more directly to the possible utility of classification in helping us better understand differences in what may possibly be different types of autism. That was the intention of my original comment. Clearly in this thread people (myself included) have talked about 2 types of labels, one that refers to levels of functioning on a particular domain, and another type that is intended to describe possible different conditions (for example the debate over High functioning vs Asperger’s).
I apologize if I offended anyone. Nestor.
Kristina Chew, PhD
Feb 13, 2008 at 12:56 am
As a further comment, no professional has said that Charlie is one “functioning level” or another. I think Charlie’s minimal language — he can talk, but is does not too much, and much of what he says is not entirely comprehensible to most people—and his significant academic struggles seems to be noted by most people fairly quickly.
Charlie’s diagnosis has been “autism,” plain and simple.
stopautismquackery
Feb 13, 2008 at 1:13 am
Dave:
I’m sorry. I don’t understand your reply, but it was not directed at all toward your son. I didn’t happen to think Chuck’s comment was “ignorant”. I don’t happen to agree with certain “descriptive terms” we were discussing and if you think that makes me a quack, well, then that’s your right.
Skov
Feb 15, 2008 at 2:07 pm
Can someone with more science knowledge help me with this…in “The Kid-Friendly ADHD and Autism Cookbook”, it talks about the “leaky gut” issue with gluten and casein and refers directly to IgG antibodies interfering with neurological functions. Do they somehow relate (from a non science perspective, it seems like they should…)?
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