title: Anti-brain antibodies are associated with more severe cognitive and behavioral profiles in Italian children with Autism Spectrum Disorder.
abstract: Circulating 45 and 62kDa antibodies targeting the cerebellum were previously associated with Autism Spectrum Disorder (ASD), lower adaptive/cognitive function and aberrant behaviors. Moreover, 37, 39 and 73kDa maternal antibodies (mAb) targeting the fetal brain were previously correlated with broad autism spectrum, irritability, abnormal brain enlargement and impaired expressive language. The present study aims towards clinically characterizing individuals with brain-targeted IgG and/or exposed to maternal antibrain antibodies in a large sample of Italian autistic children (N=355), their unaffected siblings (N=142) and mothers (N=333). The presence of patient- and mother-produced anti-brain antibodies does not confer increased risk of autism within the same sibship. However, the 45 and 62kDa antibodies are correlated with autism severity: the 45kDa Ab is associated with cognitive impairment and lower scores at the Vineland Adaptive Behavior Scales, the 62kDa Ab with motor stereotypies, while both correlate with larger head circumference (all P<0.05). On the other hand, maternal 37, 39 and 73kDa antibrain antibodies, either alone or in combination, are correlated with impaired verbal and non-verbal language development, neurodevelopmental delay and sleep/wake cycle disturbances in their autistic children (P<0.05). Presence of the 62kDa autoAb in the child is significantly associated with presence of the 39 and/or 73kDa antibodies in his/her mother. Our results confirm and extend previous observations in an ethnically distinct sample, providing further evidence of a pathomorphic role for anti-brain antibodies in autism while demonstrating their familial clustering.
authors.affiliation: Unit of Child and Adolescent NeuroPsychiatry, Laboratory of Molecular Psychiatry and Neurogenetics, University "Campus Bio-Medico", Rome, Italy.
authors.forename: I S
authors.initials: IS
authors.lastname: Piras
authors.affiliation: Department of Internal Medicine, University of California, Davis, Davis, CA, USA; University of California, Davis M.I.N.D. Institute, Davis, CA, USA; Children's Center for Environmental Health, University of California, Davis, Davis, CA, USA.
authors.forename: L
authors.initials: L
authors.lastname: Haapanen
authors.affiliation: Unit of Child and Adolescent NeuroPsychiatry, Laboratory of Molecular Psychiatry and Neurogenetics, University "Campus Bio-Medico", Rome, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Napolioni
authors.affiliation: Unit of Child and Adolescent NeuroPsychiatry, Laboratory of Molecular Psychiatry and Neurogenetics, University "Campus Bio-Medico", Rome, Italy; Department of Experimental Neurosciences, I.R.C.C.S. "Fondazione Santa Lucia", Rome, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Sacco
authors.affiliation: Department of Internal Medicine, University of California, Davis, Davis, CA, USA; University of California, Davis M.I.N.D. Institute, Davis, CA, USA; Children's Center for Environmental Health, University of California, Davis, Davis, CA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Van de Water
authors.affiliation: Unit of Child and Adolescent NeuroPsychiatry, Laboratory of Molecular Psychiatry and Neurogenetics, University "Campus Bio-Medico", Rome, Italy; Department of Experimental Neurosciences, I.R.C.C.S. "Fondazione Santa Lucia", Rome, Italy; Mafalda Luce Center for Pervasive Developmental Disorders, Milan, Italy. Electronic address: a.persico@unicampus.it.
authors.forename: A M
authors.initials: AM
authors.lastname: Persico
mesh_terms: D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D015551:Autoimmunity; D001921:Brain / Q000276:immunology*; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000276:immunology*; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D001323:Autoantibodies
keywords: Autism; Autism Spectrum Disorder; Autoantibodies; Autoimmunity; Cerebellum; Cognitive impairment; Language development; Macrocephaly; Sleep/wake cycle