Monkey business. Young rhesus monkeys that receive human antibrain antibodies in utero act oddly in social situations.
Credit: Nancy Collins/Creative Commons
Posted on 07/13/2013 2:50:19 AM PDT by neverdem
"Antibrain" antibodies that slip through the placenta from mother to fetus during pregnancy may account for roughly a quarter of autism cases, a new study suggests. Some scientists say the work could lead to a blood test that accurately predicts whether a mother will bear a child with this immune-triggered form of the disorder—a claim that's raising eyebrows among skeptics.
Autism spectrum disorder (ASD), a range of communication and social deficits estimated to affect 1 in 88 children, is now largely thought to be a neurodevelopmental malady that begins in the womb. For years, many researchers have brushed aside the idea that an out-of-whack immune response could contribute to this, preferring to focus on genetic factors that could derail typical brain development, says immunologist Judy Van de Water. Over the past decade, however, she and her colleagues at the University of California (UC), Davis, as well as several other research groups, have been slowly building a case for the role of an immune disorder in a subset of autism cases. "We just didn't quit," she says.
In 2008, Van de Water found that roughly a quarter of 61 women with autistic children carried in their blood an unusual group of antibodies—large, Y-shaped proteins with sticky ends that normally bind to and destroy foreign or potentially harmful microbes. Some of these, called autoantibodies, occasionally go rogue and attack the body's healthy cells, causing autoimmune diseases such as lupus and rheumatoid arthritis. The higher the level of autoantibodies in the mother's blood, the more severe the child's autistic symptoms, Van de Water observed. She hypothesized that these autoantibodies were attacking proteins necessary for fetal brain development.
Further studies showed that the autoantibodies do, indeed, bind to proteins contained in fetal brain tissue and that they could penetrate the fetal blood-brain barrier, a network of tightly packed blood vessels that is permeable to only certain substances. When injected into pregnant mice, the antibodies produced deficits such as impaired motor development and increased anxiety in the offspring, suggesting that they were interfering with brain development. It wasn't clear, however, which precise brain proteins the antibodies attacked and if they would have similar effects on the behavior of an animal more closely related to humans.
Two new studies by Van de Water and colleagues attempt to answer those questions. Both are published this week in Translational Psychiatry. In the first, the researchers identify six of the proteins to which the antibodies bind. All are abundant in the developing fetal brain, and "each works at some stage in the development of a neuron," Van de Water says. (This developmental specificity may partly explain why the autoantibodies don't attack a mother's own brain; the blood-brain barrier also matures to become less permeable to antibodies.) For example, cypin, one protein targeted by the autoantibodies, plays a key role in how neurons in the hippocampus, a brain area associated with memory and learning, branch out and connect to neighboring cells. Another called CRMP1 shepherds the growth and proper migration of neurons to their proper places in the brain.
In a parallel study, Van de Water's colleagues Melissa Bauman and David Amaral injected eight pregnant rhesus monkeys with antibodies extracted from the blood of mothers who have a child with autism. The researchers noted several behavioral abnormalities in the first 2 years of the young animals' lives. First, the monkey mothers that received the autoantibodies showed heightened protectiveness over their infants—a possible sign that they sensed something wrong in their young that the researchers couldn't detect. In addition, as these infants grew up, "there was a disconnect between approaching others and being approached" by their peers, Bauman says. In normal rhesus monkeys, these exchanges follow a tit-for-tat pattern, with roughly equal and reciprocal approaches. The animals whose fetal brains had been exposed to the antibodies, however, approached their peers far more often than they were approached, Bauman says—a sign that there was something socially "off" about them. Most striking was the young monkeys' behavior around strange animals, she says: They directly approached unknown animals far more often than their peers, which could be dangerous.
Bauman emphasizes that although these behaviors provide a closer match to the social deficits seen in human autism than can be observed in mice, autism is a uniquely human disorder. The odd behaviors are significant because they signal a departure from normal monkey behavior, she says.
The brains of the male monkeys whose mothers had received autoantibody injections also grew larger than those of females or controls, a pattern that mirrors abnormal brain development in human autism, Van de Water says.
"The fact that you can take these antibodies and squirt them into animals and replicate autistic behaviors is really powerful," says Kevin Becker, a geneticist and immunologist at the National Institute on Aging in Bethesda, Maryland. However, he notes that the small number of animals in the study means that although the results are "suggestive," "you don't want to write home to mom about it."
In an expanded analysis of blood samples from 246 mothers whose children have an autism spectrum disorder, Van de Water's team found that 23% had autoantibodies that recognized one or more of the six fetal brain proteins, compared with only 1% of 149 mothers who have typically developing children. Based on these results, she and her colleagues have calculated that the presence of a specific combination of these antibodies indicate a 99% likelihood of having a child with autism, Van de Water says. She and her colleagues at UC Davis are now collaborating with the company Pediatric Bioscience to develop a diagnostic test for prospective mothers that they say will be ready for use in about 18 months.
Other scientists are skeptical. Based on his own calculations using numbers provided in the study, "it looks to me like only 16.5% of the time will a positive value actually predict autism," if one takes into account the low prevalence of autism in the general population, says George Anderson, a neuroscientist at Yale University. "I'm amazed that they're going ahead at this point and trying to commercialize a test—this needs to be replicated several times."
Betty Diamond, a physician and immunologist at the Feinstein Institute for Medical Research in Manhasset, New York, agrees that "there's more work to be done," before such a diagnostic test is ready for prime time. "If you're using this to determine the likelihood that someone is going to have a child with ASD," which might influence the decision to have a baby or not, she says, "you want a very, very strong degree of certainty." However, she says, "this is a very exciting approach, because if this indeed contributes to some proportion of cases of ASD then there is a way to identify risk pregnancies and also a way to think about prevention" with drugs such as antibody blockers, or to begin early interventions, such as behavioral therapy, that have been shown to improve how autistic children fare long-term.
Ping
My friend's grandchild just went through "therapy". Nothing more than a nursery school.....with a ridiculously HIGH PAID "teacher/therapist".
She finally caught on and told them to go to hell.
So what were his symptoms?? He didn't look you in the eye...He was 4 and busy playing.
Thank you Neverdem. This is exactly what my wife has been saying for 10 years. Nearly every mother at my son’s Autism school has an Auto-immune disease. There is an epidemic of auto-immune disease that is going on under the radar. The growth in Autism is directly related.
Intriguing. But, as one scientist quoted pointed out, it’s not ready for prime time. A lot more work needs to be done, and it needs to be picked up by others. If these results are only coming from this lab, there could be something odd about this lab. (Others may be working on this, but the article didn’t mention them.)
UC Davis is my alma mater. It’s always interesting to see articles about it, even though I hardly ever know anyone mentioned in the article.
I’ll bet something similar can trigger homosexuality.
I’m in the computer industry but happened to run into Peter Gregersen, an MD researcher at North Shore LIJ. He discovered the gene for rheumatoid arthritis. NS LIJ is also the primary Autism research center for Long Island.
I told him about my situation. He agreed with my wife (a scientist herself with 3 autoimmune diseases). He wants to do more research on the connection between autoimmune diseases in mothers and children with Autism but as the article states, it’s not an avenue for funding.
I haven’t been to NSLIJ in a while. I’m going to send Dr. Gregersen this article. Hopefully there will be more research in more places.
I see that the Feinstein Institute is the new name for the North Shore LIJ research center. I’m glad they’re already looking at this research.
Agree, at least the high functioning variety IS an autoimmune disorder. I am still not convinced the extreme type of ASD is the same disorder.
All the kids at my son’s school are of the extreme variety. Some of the moms had “mystery symptoms” and didn’t realize they had an autoimmune disorder until later.
This is very interesting to me. I have Asperger’s, as does my son. My mother has been dealing with RA since her early forties, and I am now beginning to show symptoms of it as well.
When foreign substances such as bacteria and viruses enter the body, the immune system creates antibodies to tag the “infected” cells or even to destroy them. Sometimes there is an inappropriate immune system response and the antibodies wrongly “attack” an area and that is called an autoimmune disease like Lupus or Rheumatoid Arthritis.And in this article we are reading that it could even be the cause of autism.
So if antibodies form where there is a perceived need to attack a foreign substance in the body, then what is the trigger for what seems to be a radical increase in these antibodies?
Could it be the body’s reaction to the unnatural genetically modified foods (GMOs)???????
Thanks neverdem.
The “quirks” of Asperger’s are prevalent in my family. It is hereditary and is an autoimmune problem. But it appears to be a dynamic autoimmune issue. Oddly, antibiotics gives some relief, but after a point it stops working. Some doctors have treated sufferers with anti-fungal medicine with some success, but it does not work on all suffers.
The quirks can be a curse or a blessing.
See: Crypto Sensitivity Syndrome
http://www.backlash.com/content/disab/2003/rvm1203.html
He asks: Is Asperger’s/CSS caused by Liberalism?
I think he gets it.
Someone explain to me where the Autistic children were before the 70’s or so.
Babies have been born for thousands of years.
Suddenly, we have an explosion of Autistic children.
I don’t get it. Where were they for thousands of years before now???
They were probably lumped in with the broad categories of being mental retarded or developmentally delayed depending on the presence or absence of certain behavioral characteristics. Many diagnoses are still works in progress.
Bacterial molecules may prevent inflammatory bowel disease
FReepmail me if you want on or off my combined microbiology/immunology ping list.
His platelet count has been up and down since then but never low enough for another treatment.
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