A mother’s blood can carry the secret of a type of autism

Summary: Maternal autoantibody related autism spectrum disorder (MAR ASD) is characterized by specific maternal antibodies that react to certain proteins in the fetal brain. By examining plasma from expectant mothers, the researchers found that mothers with responsiveness to one of the nine MAR ASD patterns were eight times more likely to have a child diagnosed with autism.

Source: UC 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 characterized by the presence of specific maternal immune proteins known as 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 how the brain develops in offspring, leading to autism-related behaviors.

Two new studies from the UC Davis MIND Institute are broadening our understanding of this type of autism. They found support for predictive protein patterns in the blood of expectant mothers and links of MAR ASD to higher intensities of autistic traits.

MAR ASD patterns 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 the MAR ASD pattern) successfully predicts autism in previously diagnosed children.

They tested maternal blood samples collected 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 identified nine patterns related to MAR ASD. In this study, we wanted to verify the accuracy of these models in the prediction of MAR ASD. To do this, we tested plasma from pregnant mothers, collected from the Early Markers for Autism (EMA) study, “said Van de Water, senior author of the study. Van de Water is a UC Davis professor of immunology and neurodevelopment.

The study examined the plasma of 540 mothers of autistic children, 184 mothers of children with intellectual disabilities but without autism, and 420 mothers of the general population of children without autism or intellectual disability known at the time of the study.

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

The study also found that a mother with responsiveness to any of the nine MAR ASD patterns has about 8 times the chance of having an autistic child.

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

MAR ASD is similarly present in all states

Previous research found the MAR subtype of autism in 20% of a sample of autistic children from Northern California. However, 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: the Children’s Hospital of Philadelphia (CHOP) and the Arkansas Children’s Hospital and Research Institute (ACHRI).

Their study, published in The Journal of Developmental and Behavioral Pediatrics, recruited 68 mothers of autistic children between the ages of 2 and 12. The mothers provided blood samples and completed behavioral questionnaires on their children.

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

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

He found reactivity to at least one of the nine MAR ASD patterns in 10% of the autistic group. The image is in the public domain

“Our study showed similar MAR ASD frequencies in two other states similar to those 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 lead author of the study. “This suggests that the prevalence of MAR ASD is consistent across different demographics and geographic settings.”

MAR ASD and characteristics of autism

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

“The positivity of MAR ASD may be linked to more severe autism behaviors,” Angkustsiri said. “Both parental-reported SCQ and physician-assessed ADOS supported these findings.”

More studies are needed to understand why mothers develop these antibodies and how long these antibodies can persist. Tests for MAR ASD models can be used to assess the likelihood of a child having autism before the features are present. Researchers aim to develop an accurate clinical test to provide doctors with more tools for early diagnosis of ASD.

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

Co-authors of the Van de Water 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.

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

See also

The co-authors of Angkustsiri’s 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 IDDRC (P50HD103526) funded by the NICHD

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

About this autism research news

Author: Nadine Yehya
Source: UC Davis
Contact: Nadine Yehya – UC Davis
Image: The image is in the public domain

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


Abstract

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

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

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

The aim 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 specimens collected before delivery.

We used prenatal plasma from mothers of autistic children with or without concomitant intellectual disability (ASD = 540), intellectual disability without autism (ID = 184) and general population controls (GP = 420) collected from Early Markers for Autism (EMA ). ) she studies.

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, 95% confidence interval (CI) 3.32 to 22.43; ASD vs ID: OR = 2.77, 95% CI (1.19-7.47)) demonstrating that MAR ASD patterns are strongly associated to the ASD group and could be used to assess the risk of ASD prior to 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).

Furthermore, we found that many of these specific patterns of ASD MAR were strongly associated with ASD with intellectual disability (ASD + ID) and others associated with ASD without ID (ASD-no ID). Prenatal screening for these MAR patterns can lead to early identification of ASD and facilitate access to appropriate early intervention services based on each child’s needs.