Maternal autoantibodies are associated with abnormal brain enlargement in a subgroup of children with autism spectrum disorder |
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| Affiliation: | 1. The M.I.N.D. Institute, University of California at Davis, School of Medicine, Sacramento, CA 95817, USA;2. Department of Psychiatry and Behavioral Sciences, University of California at Davis, School of Medicine, Sacramento, CA 95817, USA;3. Department of Internal Medicine, University of California at Davis, School of Medicine, Davis, CA 95616, USA;4. Department of Public Health Sciences, Division of Biostatistics, University of California at Davis, Davis, CA 95616, USA;1. University of California, San Diego, School of Medicine, Department of Pediatrics/Rady Children''s Hospital San Diego, La Jolla, CA 92093, USA;2. Department of Cellular & Molecular Medicine, Stem Cell Program, MC 0695, La Jolla, CA 92093, USA;3. University of California, San Diego, Department of Anthropology, 9500 Gilman Drive, La Jolla, CA 92093, USA;4. Center for Academic Research and Training in Anthropogeny (CARTA), University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA;5. Neuroscience Graduate Program, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA;1. University Clinics of Child and Adolescent Psychiatry, University of Zurich, Neumünsterallee 9, 8032 Zurich, Switzerland;2. Neuroscience Center Zurich, University of Zurich and ETH Zurich, Switzerland;3. Laboratory for Experimental Feto-Maternal Medicine, University Medical Center Hamburg, Hamburg, Germany;4. Department of Psychosomatics and Psychiatry, University Children''s Hospital Zurich, Zurich, Switzerland;5. Department of Psychosomatic Medicine and Psychotherapy, University Medical Center Hamburg, Hamburg, Germany;1. Department of Pharmacology, 500 University Drive, Penn State College of Medicine, Hershey, PA 17033, USA;2. Department of Physiology, BMSB 653, P.O. Box 26901, Oklahoma University Health Sciences Center, Oklahoma City, OK 73216, USA;3. Reynolds Oklahoma Center on Aging, SLY-BRC 1370, 975 NE 10th St, Oklahoma City, OK 73104, USA;4. Penn State Hershey Eye Center, 500 University Drive, Penn State College of Medicine, Hershey, PA 17033, USA;5. Department of Cellular and Molecular Physiology, 500 University Drive, Penn State College of Medicine, Hershey, PA 17033, USA;1. Institute for Advanced Physics and Mathematics, Zhejiang University of Technology, Hangzhou 310032, China;2. Division of Human Support System, Faculty of Symbiotic Systems Science, Fukushima University, Fukushima 960-1296, Japan;3. Department of Physics, Science and Research Branch, Azad University, Tehran 1477893855, Iran |
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| Abstract: | Autism spectrum disorder (ASD) is very heterogeneous and multiple subtypes and etiologies likely exist. The maternal immune system has been implicated in the pathogenesis of some forms of ASD. Previous studies have identified the presence of specific maternal IgG autoantibodies with reactivity to fetal brain proteins at 37 and 73 kDa in up to 12% of mothers of children with ASD. The current study evaluates the presence of these autoantibodies in an independent cohort of mothers of 181 preschool-aged male children (131 ASD, 50 typically developing (TD) controls). We also investigated whether ASD children born to mothers with these autism-specific maternal IgG autoantibodies exhibit a distinct neural phenotype by evaluating total brain volume using structural magnetic resonance imaging (MRI). Of the 131 ASD children, 10 (7.6%) were born to mothers with the 37/73 kDa IgG autoantibodies (ASD-IgG). The mothers of the remaining ASD children and all TD controls were negative for these paired autoantibodies. While both ASD groups exhibited abnormal brain enlargement that is commonly observed in this age range, the ASD-IgG group exhibited a more extreme 12.1% abnormal brain enlargement relative to the TD controls. In contrast, the remaining ASD children exhibited a smaller 4.4% abnormal brain enlargement relative to TD controls. Lobar and tissue type analyses revealed that the frontal lobe is selectively enlarged in the ASD-IgG group and that both gray and white matter are similarly affected. These results suggest that maternal autoantibodies associated with autism spectrum disorder may impact brain development leading to abnormal enlargement. |
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