A mother’s blood may hold the secret to a type of autism

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Summary: Maternal Autoantibody Related Autism Spectrum Disorder (ASD MAR) is marked by specific maternal antibodies that react to certain proteins in the fetal brain. By examining the plasma of pregnant women, the researchers found that mothers responding to one of nine ASD MAR models were eight times more likely to have a child diagnosed with autism.

Source: U.C. Davis

Autism is a neurodevelopmental condition affecting 1 in 44 children in the United States. It has a wide range of characteristics with different intensities and causes. One type of autism is maternal autoantibody-related autism spectrum disorder (MAR ASD).

MAR ASD is marked by the presence of specific maternal immune proteins called autoantibodies that react to certain proteins present in the fetal brain. Maternal autoantibodies (IgG) cross the placenta and enter the developing brain. Once there, they can cause changes in the way the brain develops in offspring, leading to behaviors linked to autism.

Two new studies from the UC Davis MIND Institute expand our understanding of this type of autism. They found support for predictive protein patterns in the blood of pregnant women and links between MAR ASD and higher intensities of autistic traits.

MAR ASD models linked to autism before birth

Judy Van de Water of the MIND Institute and a team of researchers have shown that binding of autoantibodies to nine specific combinations of proteins (known as MAR ASD patterns) successfully predicts autism in children previously diagnosed.

They tested maternal blood samples taken during pregnancy to see if they could validate the identified patterns. They wanted to see if the models accurately predicted autism in children.

The results of their study were published in Molecular psychiatry.

“Previously, we had identified nine patterns related to MAR ASD. In this study, we wanted to verify the accuracy of these patterns in predicting MAR ASD. To do this, we tested plasma from pregnant women, collected by the Early Markers for Autism (EMA) study,” said Van de Water, the study’s lead author. Van de Water is a professor of immunology and neurodevelopment at UC Davis.

The study examined the plasma of 540 mothers of children with autism, 184 mothers of children with intellectual disabilities but no autism, and 420 mothers from the general population of children without known autism or intellectual disabilities at the time of the study. study.

He found reactivity to at least one of the nine ASD MAR patterns in 10% of the autistic group. This is compared to 4% of the developmental disability group for some models and 1% of the general population group. Four patterns were only present in mothers whose children were later diagnosed with autism, making these particular autoantibody patterns highly predictive.

The study also found that a mother responding to one of the nine ASD MAR models is about 8 times more likely to have an autistic child.

Several MAR ASD patterns were strongly associated with autism with intellectual disability. Others were linked to autism without intellectual disability. The protein profile most strongly linked to autism was (CRMP1+CRMP2). It increased the likelihood of an autism diagnosis 16-fold and was not found in non-autistic groups.

MAR ASD similarly present in all states

Previous research has found the MAR autism subtype in 20% of a sample of autistic children in Northern California. Yet, until now, this type of autism has not been studied in any state other than California.

A team of researchers led by Kathleen Angkustsiri explored MAR ASD at two new clinical sites: Children’s Hospital of Philadelphia (CHOP) and Children’s Hospital and Research Institute of Arkansas (ACHRI).

Their study, published in The Journal of Developmental and Behavioral Pediatrics, recruited 68 mothers of autistic children aged 2 to 12. Mothers provided blood samples and completed behavioral questionnaires about their children.

The study also included data from the children’s clinical diagnostic assessments. He used established diagnostic measures known as ADOS (the Autism Diagnostic Observation Schedule) and the Social Communication Questionnaire (SCQ) to assess children’s autistic characteristics.

MAR ASD was present in 21% of CHOP samples and 26% of ACHRI samples. Overall, 23.5% of blood samples were considered MAR positive (+ MAR), showing autoantibodies reacting to known MAR ASD protein profiles.

This shows blood test tubes
He found reactivity to at least one of the nine ASD MAR patterns in 10% of the autistic group. Image is in public domain

“Our study showed similar MAR ASD frequencies in two other states similar to what we observed in Northern California,” Angkustsiri said. Angkustsiri is an associate professor of developmental-behavioral pediatrics at UC Davis Children’s Hospital and the UC Davis MIND Institute and the study’s lead author. “This suggests that the prevalence of MAR ASD is consistent across different demographics and geographies.”

MAR ASD and Autism Features

The study also looked at the link between MAR ASD and autism severity. It showed that children of mothers with +MAR antibodies had higher autism severity scores than those of -MAR mothers. He found no significant differences in their IQ, adaptive function, or unusual behavior.

“MAR ASD positivity may be linked to more severe autistic behaviors,” Angkustsiri said. “Parent-reported SCQ and clinician-rated ADOS supported these findings.”

Further study is needed to understand why mothers develop these antibodies and how long these antibodies can persist. The MAR ASD Patterns Test can be used to assess the likelihood that a child has autism before the features are present. The researchers aim to develop an accurate clinical test to provide clinicians with more tools for earlier diagnosis of ASDs.

“We hope our work can help develop services that are better tailored to the specific type of autism, strengths and challenges of the child,” Van de Water said.

Co-authors of Van de Water’s study are Alexandra Ramirez-Celis, Joseph Schauer and Paul Ashwood of UC Davis, Lisa Croen, Cathleen Yoshida and Stacey Alexeeff of Kaiser Permanente, and Robert Yolken of Johns Hopkins University. .

Funding: Funding was provided by NIEHS Center for Children’s Environmental Health and Environmental Protection Agency (EPA) Grants (2P01ES011269-11, 83543201), NIEHS-funded EMA Study (R01ES016669), NICHD-funded IDDRC ( P50HD103526) and the Consejo Nacional de Ciencia y Tecnologia (CONACYT- UC MEXUS) Doctoral scholarships.

See also

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The co-authors of the Angkustsiri study are Jill Fussell, Amanda Bennett, Joseph Schauer, Alexandra Ramirez-Celis, Robin Hansen and Judy Van de Water. The study was funded by the DBPNet Young Investigator Award UT5MC42432 and the NICHD-funded IDDRC (P50HD103526)

The authors acknowledge that medical terms such as “symptom” and “severity” are pathologizing and strive to move away from this historical terminology. In this article, the analysis is based on the “calibrated severity score” generated from using the ADOS diagnostic test, which is why they use them in this case.

About this autism research news

Author: Nadine Yehya
Source: U.C. Davis
Contact: Nadine Yehya – UC Davis
Image: Image is in public domain

Original research: Free access.
“Maternal autoantibody profiles as biomarkers for ASD and ASD with concurrent intellectual disability” by Judy Van de Water et al. Molecular psychiatry


Summary

Maternal autoantibody profiles as biomarkers for ASD and ASD with concurrent intellectual disability

Maternal autoantibody-related ASD (MAR ASD) is a subtype of autism in which pathogenic maternal autoantibodies (IgG) cross the placenta, gain access to the developing brain, and cause neurodevelopmental alterations and behaviors associated with autism in exposed offspring.

We have previously reported a maternal IgG response to eight proteins (CRMP1, CRMP2, GDA LDHA, LDHB, NSE, STIP1 and YBOX) and this reactivity to nine specific combinations of these proteins (MAR ASD models) was predictive of ASD risk.

The objective of the present study was to validate the previously identified MAR ASD models (CRMP1 + GDA, CRMP1 + CRMP2, NSE + STIP1, CRMP2 + STIP1, LDHA + YBOX, LDHB + YBOX, GDA + YBOX, STIP1 + YBOX and CRMP1 + STIP1) and their accuracy in predicting the risk of ASD in a prospective cohort using maternal samples taken before parturition.

We used prenatal plasma from mothers of autistic children with or without concurrent intellectual disability (ASD = 540), intellectual disability without autism (ID = 184) and controls from the general population (GP = 420) collected by the markers Early Autism (EMA) study.

We found reactivity to one or more of the nine previously identified MAR ASD patterns in 10% of the ASD group versus 4% of the ID group and 1% of the GP controls (ASD vs GP: Odds Ratio (OR) = 7.81, Range (95% confidence (CI) 3.32-22.43; ASD vs ID: OR = 2.77, 95% CI (1.19-7.47)) demonstrating that ASD MAR patterns are strongly associated to the ASD group and could be used to assess the risk of ASD before the onset of symptoms.

The pattern most strongly associated with ASD was CRMP1 + CRMP2 and increased the odds of an ASD diagnosis 16-fold (3.32 to >999.99).

Additionally, we found that several of these specific patterns of MAR ASD were strongly associated with ASD with intellectual disability (ASD+DI) and others associated with ASD without DI (ASD without DI). Prenatal screening of these MAR patterns can lead to earlier identification of ASDs and facilitate access to appropriate early intervention services based on each child’s needs.

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