AAt the turn of the 21st century, the prevalence of autism spectrum disorder among American children was approximately 1 in 150. That’s according to to data collected by the U.S. Centers for Disease Control and Prevention’s Autism and Developmental Disabilities Monitoring Network. A decade later, in 2010, the prevalence increased to 1 in 68 children. In 2020, the number rose again – to 1 in 36 children. “The prevalence of Autism Spectrum Disorder (ASD) has increased dramatically in recent decades, supporting the claim of an autism epidemic,” the paper’s authors wrote. a 2020 study in the diary Brain Sciences.
The precise cause and extent of this epidemic are disputed. Some researchers observed that the diagnostic criteria for ASD have evolved over this period – broadening and broadening to include a wider range of conditions. And so some of the increase in diagnoses, they argue, is likely attributable to expanded conceptions and a deeper understanding of autism. Still, the increasing prevalence of ASD diagnoses has stimulated greater scientific interest in the underlying causes of the disorder. This work revealed a possible connection between ASD and autoimmune diseases, including systemic lupus erythematosus (SLE).
“There has been a link for some time between maternal autoimmune diseases and the risk of having a child with autism,” says Paul Ashwood, professor of medical microbiology and immunology at the University of California, Davis and the MIND Institute, which focuses on autism and other neurodevelopmental conditions. He mentions work based on national data collected over many years from mothers and their children in Denmark. What to look for found that prenatal exposure to a number of different maternal autoimmune diseases, including lupus and rheumatoid arthritis, was associated with an increased risk of an eventual autism diagnosis.
Since then, more research has confirmed the apparent association and also found evidence of a broader link between a pregnant woman’s immune system and a child’s risk of autism. “What we’ve been looking at a lot more recently is how anything that generates a maternal immune response can be linked to autism risk,” says Ashwood.
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Antibodies and the developing brain
In response to a threat, such as a virus or other pathogen, the immune system produces protein antibodies designed to neutralize or eliminate the danger. But among people with autoimmune diseases such as systemic lupus erythematosus, the immune system produces antibodies that attack the body’s own healthy proteins or tissues. These are called autoantibodies.
In a 2015 study in the diary Arthritis and Rheumatology, a group of Canadian researchers found that children born to women with systemic lupus erythematosus were almost twice as likely to develop autism as children born to women who did not have SLE. Furthermore, children of mothers with SLE tend to be diagnosed with autism at a younger age than children of mothers without SLE.
“In utero exposures to maternal antibodies and cytokines [proteins that regulate the growth of immune system cells] are important risk factors for ASD,” the authors of that study wrote. Women with SLE “present high levels of autoantibodies and cytokines,” which have been shown in animal models to alter fetal brain development and induce behavioral abnormalities in offspring, they added.
“Maternal antibodies, including autoantibodies, begin to cross the placental barrier around day 100 of pregnancy, and we know that this can affect the developing fetus,” he says. Judy Van Waterprofessor of medicine and associate director of biological sciences at the University of California, Davis and the MIND Institute. “One of the things we’re looking at is how these autoantibodies or other aspects of the mother’s immune response might affect neurodevelopment.”
Some to look for has already discovered that maternal autoantibodies related to SLE can lead to the development of heart problems and also blood and liver abnormalities in a developing fetus. Van de Water and her colleagues are examining whether and how other autoantibodies might similarly affect fetal brain development. “Several of the proteins that these autoantibodies target are actually highly expressed in the developing brain rather than the mature brain,” she says. This can create unique exposure risks for a developing fetus.
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The immunoautism link
In addition to lupus, many others maternal autoimmune diseases, including rheumatoid arthritis, have been linked to an increased risk of having children with autism. The same applies to illnesses related to the immune system, such as asthma and allergies. Van de Water and other researchers are now taking a broader look at how the activity of a pregnant woman’s immune system can affect the fetal brain. “Anything that affects maternal immune homeostasis or the balance of the mother’s immune response can impact the child’s neurodevelopment,” she says. “So we’re looking at different responses of the immune system – what the response is, how intense the response is, the makeup of the inflammatory markers – and their relationships to autism.”
An autoimmune disease like lupus is a source of a heightened maternal immune response, but Van de Water says that under the right conditions, virtually anything that triggers an immune reaction can potentially affect neurodevelopment in ways that contribute to autism. “We’re seeing a lot of different maternal immune activations or disruptions — whether it’s due to an existing condition or disease, or something that happens during pregnancy,” she says.
In particular, experts highlight the role that inflammatory cytokines may play in autism risk. “The way to think about cytokines in the fetal environment is that they can potentially act in a dose-response manner – just as too much is bad, so too little is also bad, but there is this level of goldilocks that you need to have to be safe. suit. growth,” says Ashwood. “If there is some type of immunological condition or inflammatory response that leads to the constant production and release of these cytokines, they can cross the placental barrier and affect fetal development.”
In the brain, for example, the presence of cytokines “could affect the growth of neurons, the proliferation of neurons, the connection of neurons with other neurons, the formation of synapses, neuronal migration and all kinds of processes that are necessary to build an interconnected network as the brain grows”, he explains. “Having these systems slightly imbalanced can potentially affect the trajectory of neurodevelopment.”
Lupus and other autoimmune diseases are a potential source of cytokine imbalance. But Van de Water says obesity is another inflammation-related condition — and much more common than lupus — that could produce the kind of immune activity that contributes to autism. “Obesity has a major inflammatory component associated with it,” she says. “We just published A paper Looking at this, it turns out that the biggest maternal risk factor for autism was not any autoimmune disease, but asthma and allergies associated with obesity. If you combine these two factors with obesity, the risk will be significantly higher.”
Another potential link between a mother’s immune activity and her children’s risk of autism is the microbiome – the community of bacteria that inhabit the gut. Some research has found that metabolites produced by the mother’s intestinal bacteria can affect the neurodevelopment of the fetus. Furthermore, there is evidence that infections, metabolic stress (such as obesity), and other immune-related events can lead to maternal microbiome imbalances that could potentially increase their children’s risk of autism.
What is more, there is evidence that people with autism share some distinct microbiome characteristics and that gut-related symptoms – diarrhea, constipation and abdominal pain in particular – are common comorbidities among people with autism. “There is a lot of interest right now in the microbiome – how it is formed, how it nourishes the body and how it shapes the activity of the immune system,” says Ashwood. There has also been a lot of recent interest in the so-called “gut-brain connection” and science has established that the intestinal microbiota influences brain connectivity and functioning.
It is not yet certain, but it is possible that maternal autoimmune diseases and other disorders related to the immune system could directly or indirectly affect the fetal microbiome in ways that contribute to the development of autism.
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A multifaceted disease
While there are several plausible mechanisms that could link autoimmune diseases to autism, experts say this is likely only a small part of the autism equation. “It’s worth remembering that autoimmunity in the general population is quite low,” says Ashwood. Also, to look for on the link between maternal lupus and autism found that although the risks are high, women with the autoimmune disease still have a low overall risk of having a child with autism.
In addition to maternal immunological conditions, there is a growth evidence of the role that genetics plays in a person’s risk of autism. “More than 100 genes are known to confer risk, and 1,000 or more can be identified,” wrote David Amaral, a distinguished professor at the University of California, Davis and the MIND Institute, in a 2017 article about the causes of autism. He goes on to explain that, most likely, a mix of genetic and environmental factors contribute to the development of autism. “It seems clear at this point,” he writes, “that when all is said and done, we will discover that autism has multiple causes that occur in diverse combinations.”
Van de Water also emphasizes this point. Autism spectrum disorder is a diverse and multifaceted condition, and its underlying causes are likely equally complex. Lupus and other immune-related diseases may be a piece of the puzzle, but they are just one of many. “Anyone who says they know the cause of autism doesn’t know autism very well. There are many layers,” says Van de Water. “There appears to be a relationship between a mother’s immune activity and autism, but we don’t have all the answers yet.”
This story originally appeared on Time.com read the full story
