Two studies indicate that autoantibodies in maternal blood may provide diagnostic clues in autism

Certain patterns of proteins in the blood of pregnant women may help to predict one type of autism spectrum disorder (ASD) in children, according to two new studies.

Both studies focused on maternal auto-antibody-related autism spectrum disorder, or MAR ASD. In this type of autism, specific maternal immune proteins known as autoantibodies cross the placenta and react to certain proteins found in the fetal brain. This may affect brain development, leading to behaviors linked to ASD.

In the first study, conducted in California, Alexandra Ramirez-Celis and colleagues tested maternal blood samples collected during pregnancy from 540 mothers of children with ASD, 184 mothers of children with intellectual disability (ID) but without ASD, and 420 controls. The researchers found that autoantibody binding to nine specific combinations of proteins (known as MAR ASD patterns) successfully predicted autism in previously diagnosed children.

The researchers detected reactivity to at least one of the nine MAR ASD patterns in 10 percent of the ASD group, compared with 4 percent of the ID group and 1 percent of controls. Four patterns were seen only in mothers whose children were later diagnosed with ASD, making those particular autoantibody patterns highly predictive.

The researchers also found that a mother with reactivity to any one of the nine MAR ASD patterns had an approximately eight-fold higher chance of having an autistic child. The pattern most strongly linked to ASD, called CRMP1+CRMP2, increased the odds of an ASD diagnosis by 16 times and was not detected in the non-ASD groups.

The researchers conclude, “Prenatal screening for these MAR patterns may lead to earlier identification of ASD and facilitate access to the appropriate early intervention services based on each child’s needs.”

In the second study, Kathleen Angkustsiri and colleagues analyzed blood samples from mothers of children with ASD in Pennsylvania and Arkansas to see if the findings from the California research could be duplicated. In this study, 68 mothers of children with ASD provided blood samples and completed behavioral questionnaires about their children. The researchers also used two diagnostic measures, the Autism Diagnostic Observation Schedule (ADOS) and the Social Communication Questionnaire (SCQ). to assess the children.

The researchers found that MAR ASD was present in 21 percent of the samples from Pennsylvania and 26 percent of the samples from Arkansas. Overall, 23.5 percent of the blood samples were found to be MAR positive. Angkustsiri says, “Our study showed… MAR ASD frequencies in two other states similar to what we observed in Northern California. This suggests that the prevalence of MAR ASD is consistent across different demographics and geographic settings.”

Angkustsiri and colleagues also found that children of mothers positive for MAR antibodies had higher autism severity scores than children of mothers without these antibodies. However, they did not find significant differences in these children’s IQ, adaptive functioning, or behavior. The researchers say additional study is needed to understand why mothers develop MAR antibodies and how long these antibodies persist.

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“Maternal autoantibody profiles as biomarkers for ASD and ASD with co-occurring intellectual disability,” Alexandra Ramirez-Celis, Lisa A. Croen, Cathleen K. Yoshida, Stacey E. Alexeeff, Joseph Schauer, Robert H. Yolken, Paul Ashwood, and Judy Van de Water, Molecular Psychiatry, May 26, 2022 (free online). Address: Judy Van de Water, javandewater@ucdavis.edu.

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“Pilot study of maternal autoantibody–related autism,” Kathleen Angkustsiri, Jill J. Fussell, Amanda Bennett, Joseph Schauer, Alexandra Ramirez-Celis, Robin L. Hansen, and Judy Van de Water, Journal of Developmental & Behavioral Pediatrics, May 13, 2022 (online). Address: Kathleen Angkustsiri, Developmental Behavioral Pediatrics, Department of Pediatrics, University of California Davis Health, 2825 50th St, Sacramento, CA 95817, kangkustsiri@ucdavis.edu.

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“Mother’s blood may carry the secret to one type of autism,” news release, UC Davis, June 23, 2022

This article originally appeared in Autism Research Review International, Vol. 36, No. 3, 2022