Journal
BRAIN BEHAVIOR AND IMMUNITY
Volume 38, Issue -, Pages 91-99Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbi.2013.12.020
Keywords
Autism; Autism Spectrum Disorder; Autoantibodies; Autoimmunity; Cerebellum; Cognitive impairment; Language development; Macrocephaly; Sleep/wake cycle
Categories
Funding
- Italian Ministry for University, Scientific Research and Technology (PRIN) [2006058195, 2008BACT54_002]
- Italian Ministry of Health [RFPS-2007-5-640174, RF-2011-02350537, CCM2012-Progetto NIDA]
- Fondazione Gaetano e Mafalda Luce (Milan, Italy)
- Autism Aid ONLUS (Naples, Italy)
- Autism Speaks (Princeton, NJ)
- Autism Research Institute (San Diego, CA)
- Innovative Medicines Initiative Joint Undertaking (EU-AIMS) [115300]
- NIEHS [1 P01 ES11269-01, 1 R01-ES015359]
- U.S. Environmental Protection Agency (U.S.EPA) through the Science to Achieve Results (STAR) program [R829388]
- UC Davis M.I.N.D. Institute
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Circulating 45 and 62 kDa antibodies targeting the cerebellum were previously associated with Autism Spectrum Disorder (ASD), lower adaptive/cognitive function and aberrant behaviors. Moreover, 37, 39 and 73 kDa 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 62 kDa antibodies are correlated with autism severity: the 45 kDa Ab is associated with cognitive impairment and lower scores at the Vineland Adaptive Behavior Scales, the 62 kDa Ab with motor stereotypies, while both correlate with larger head circumference (all P < 0.05). On the other hand, maternal 37, 39 and 73 kDa 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 62 kDa autoAb in the child is significantly associated with presence of the 39 and/or 73 kDa 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 antibrain antibodies in autism while demonstrating their familial clustering. (C) 2014 Elsevier Inc. All rights reserved.
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