Maternal blood can reveal the secret of some types of autism

Summary: Autism spectrum disorder (MAR ASD) due to maternal autoantibodies is characterized by specific maternal antibodies that react to specific proteins in the fetal brain. By examining the plasma of expectant mothers, the researchers found that mothers with reactivity to one of the nine MAR ASD samples were eight times more likely to have a child diagnosed with autism.

A source: UC Davis

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

MAR ASD is characterized by the presence of maternal immune proteins known as autoantibodies that react to certain proteins found in the fetal brain. Maternal autoantibodies (IgG) cross the placenta and reach the developing brain. Once there, they can make changes in the developmental lineage of the offspring and lead to autism-related behaviors.

Two new studies by the UC Davis MIND Institute expand our understanding of this type of autism. They found support for protein patterns in the blood of expectant mothers and a link between MAR ASD and high-intensity autistic traits.

MAR ASD patterns were associated with autism before birth

Judy Van de Waters of the MIND Institute and a team of researchers have shown that autoantibodies associated with nine specificity of protein combinations (known as MAR ASD samples) can successfully predict autism in children previously diagnosed.

They tested the identified samples and tested the mother’s blood samples collected during pregnancy to see if they could. They wanted to see if the models accurately predicted autism in children.

The results of their study were published Molecular psychiatry.

“Previously, we identified nine patterns associated with MAR ASD. In this study, we wanted to verify the accuracy of these models in advance of MAR ASD. To do this, we tested plasma from pregnant mothers collected by the Early Autism Markers (EMA) study, ”said Van de Water, the study’s lead author. Van de Water is a professor of immunology and neuronal development at Davis University.

The study tested the plasma of 540 mothers of children with autism, 184 mothers of children with dementia but not autism, and 420 mothers of children with no autism or mental disorders.

He found that 10% of the autistic group had reactivity to at least one of the nine MAR ASD samples. This is comparable to 4% of the group with mental disorders in some models and 1% of the general population. Only mothers whose children were later diagnosed with autism had four samples, which allowed them to predict specific samples of autoantibodies.

The study also found that a mother with a reaction to one of nine MAR ASD samples had an 8-fold chance of having an autistic child.

Several MAR ASD models have been associated with autism in mental disorders. Others are associated with autism without mental disorders. The protein pattern most closely associated with autism was (CRMP1 + CRMP2). This increased the diagnosis of autism by 16 times and was not found in non-autism groups.

MAR ASD is the same in all states

Previous studies have found a MAR subtype of autism in 20% of autistic children in Northern California. However, to date, this type of autism has not been studied in any state other than California.

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

Their study was published Journal of Development and Behavioral Pediatrics, It employs 68 mothers of autistic children aged 2 to 12 years. Mothers submitted blood samples and filled out a questionnaire on their children’s behavior.

The study also includes data from clinical diagnostic assessments in children. He used established diagnostic measures called ADOS (Autism Diagnostic Monitoring Schedule) and Social Communication Questionnaire (SCQ) to assess children’s autistic characteristics.

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

He found that 10% of the autistic group had reactivity to at least one of the nine MAR ASD samples. Image in public domain

“Our study showed a similar MAR ASD frequency in the other two states observed in Northern California,” Angkussiri said. Angkussiri is an associate professor of developmental-behavioral pediatrics at UC Davis Children’s Hospital and UC Davis MIND Institute and co-author of the study. “This shows that the prevalence of MAR ASD is consistent across different demographic and geographical conditions.”

Features of MAR ASD and autism

The study also examined the link between MAR ASD and the severity of autism. This showed that children of mothers with + MAR antibodies had higher autism severity scores than -MAR mothers. It did not find significant differences in their IQ, adaptive function, or abnormal behavior.

“MAR ASD positivity may be related to severe autism behavior,” Angkussiri said. “Both SCQ reported by parents and ADOS evaluated by clinics supported these results.”

Further research is needed to understand why these antibodies are formed in mothers and how long these antibodies can persist. MAR can be used to assess the likelihood that a child will develop autism before testing features for ASD samples are available. Researchers aim to develop an accurate clinical test to provide clinics with more tools for early diagnosis of ASD.

“We hope that our work will help to develop better tailored services based on the type of autism and the child’s strengths and unique challenges,” Van de Water said.

The authors of the Van de Waot study are Alexandra Ramirez-Selis, Joseph Schauer and Paul Ashwood UC Davis, Lisa Crowen, Kathleen Yosida and Stacey Alexeis Kaiser from Permanent, and Robert Yolken from Johns Hopkins University.

Funding: Funding NIEHS Children’s Environmental Health and Environmental Protection Agency (EPA) grants (2P01ES011269-11, 83543201), NIEHS-funded EMA study (R01ES016669), NICHD-funded NIHA. and Technology (CONACYT-UC MEXUS) doctoral scholarships.

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

The authors acknowledge that medical terms such as “symptom” and “severity” lead to a pathological condition and try to avoid this historical terminology. The analysis in this article is based on the “calibrated gravity score” resulting from the use of the ADOS diagnostic test, so they are using them in this case.

It’s about autism research news

Author: Nadine John
A source: UC Davis
The connection: Nadine Yahya – UC Davis
Photo: Image in public domain

Original study: Open access.
Judy Van de Water Molecular psychiatry


Abstract

Maternal autoantibody profiles as a biomarker for ASD and ASD along with mental disorders

Maternal antibody-associated ASD (MAR ASD) is a type of autism in which pathogenic maternal autoantibodies (IgG) can cross the placenta and enter the developing brain and cause autism-related neuronal changes and behavior in sick offspring.

We previously reported maternal responses to eight proteins (CRMP1, CRMP2, GDA, LDHA, LDHB, NSE, STIP1, and YBOX) and predicted ASD risk for reactivity to nine specific combinations of these proteins (MAR ASD samples).

The purpose of the present study was to test previously identified MAR ASD samples (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 prospective cohorts using maternal samples collected before delivery.

We used the perinatal plasma of mothers of autistic children with or without mental disorders (ASD = 540), collected by early markers of autism (EMA), non-autistic mental disorders (ID = 184), and general population control (GP = 420). )) to read.

We found reactivity to one or more of the nine previously identified MAR ASD samples in 10% of the ASD group compared to 4% of the ID group and 1% of the GP controls (ASD vs GP: Odds Ratio (OR) = 7.81, 95% confidence interval (CI) 3.32 to 22.43; ASD vs ID: OR = 2.77.95% CI (1.19–7.47) indicates that MAR ASD samples are closely related to the ASD group and can be used to assess ASD risk. onset of symptoms.

The strongest pattern associated with ASD was CRMP1 + CRMP2, which increased the probability of diagnosing ASD by 16 times (from 3.32 to> 999.99).

In addition, we found that several of these specific MAR ASD models were associated with ASD associated with ASD (ASD + ID) and ID-associated ASD (ASD-free ID). This prenatal screening for MAR samples can lead to early detection of ASD and facilitate access to appropriate early intervention services based on each child’s needs.

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