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Antibodies Reacting to Brain Tissue in Basque Spanish Children with Autism Spectrum Disorder and Their Mothers

Thursday, 2 May 2013: 14:00-18:00
Banquet Hall (Kursaal Centre)
C. C. Rossi1, J. Fuentes2, J. Van de Water3 and D. G. Amaral4, (1)University of Colorado Anschutz Medical Campus, Aurora, CO, (2)Policlinica Gipuzkoa, San Sebastian, Spain, (3)The M.I.N.D. Institute, University of California, Davis, Sacramento, CA, (4)M.I.N.D. Institute and Department of Psychiatry and Behavioral Sciences, University of California Davis Medical Center, Sacramento, CA
Background:  Previous investigations found that a subset of children with autism spectrum disorder (ASD) in California possessed plasma autoantibodies that reacted intensely with brain interneurons or other neural profiles.  Moreover, for several cohorts of American women, maternal autoantibody reactivity to specific fetal brain proteins was highly specific to mothers of children with ASD.

Objectives:  We sought to determine whether children with ASD and their mothers from a regionally specific cohort from the Basque Country of Spain demonstrated similar reactivity.

Methods:  Thirty-seven subjects with ASD from Gautena (the regional program for ASD in the Gipuzkoa province of Spain) and 37 typically developing matched subjects from the local schools participated, along with the mothers of each subject and siblings of children with ASD. Children’s samples were immunohistochemically reacted in California with sectioned rhesus macaque brain tissue, and plasma IgG reactivity to brain proteins was measured using western blot technology.  Plasma samples were processed and evaluated in an identical manner to what was done in previous studies. 

Results:  Plasma from 22% of subjects with ASD and 19% of typically developing controls reacted to brain interneurons.  One subject with ASD and one control subject displayed plasma reactivity to brain nuclei (representing 3% of subjects in both groups), and plasma from one subject with ASD reacted to beaded axons.  No difference in the occurrence of brain reactivity was observed between subjects with and without ASD.  Siblings of children with ASD were screened for ASD and each received a score below the cutoff that would indicate a suspicion of ASD.  They did not differ significantly from children with ASD or typical controls with respect to plasma reactivity to cerebellar proteins.  Five percent of maternal samples from mothers of children with ASD reacted to fetal brain proteins at 37 and 73 kDa, and 3% of samples from mothers of children with ASD reacted to fetal brain proteins at 39 and 73 kDa.  These combinations were exclusively observed in mothers of children with ASD.  While the occurrence of these two combinations did not differ significantly between the two maternal groups in the current study, the findings are consistent with previous studies (in which reactivity to these combinations was exclusively found in mothers of children with ASD) that did reach significance. 

Conclusions:  Reactivity of children’s plasma samples did not differ based on a diagnosis of ASD.  The percentage of children in the Spanish sample (both with and without ASD) whose plasma reacted intensely with inerneurons was the same as that observed in a recent analysis of American children enrolled in the Autism Phenome Project, but was lower than an earlier American sample of similarly aged subjects.  A comparison of the current findings with several previous studies with regard to maternal plasma immunoreactivity suggest that two combinations of reactivity – to proteins at 37 and 73 kDa or 39 and 73 kDa – are specific to mothers of children with ASD across different populations.  

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