The Presence of Antibodies against Differentiating Neuronal Progenitors in Sera FromChildren with Autism

Background: It has been hypothesized that altered brain development during embryogenesis and early postnatal life is responsible for the abnormal behaviors seen in autism. However, the specific pathological mechanisms that influence early development remain unidentified.  Because of the presence of autoantibodies against brain tissue in sera from children with autism, damage of the brain-blood barrier and abnormal autoimmune responses were suggested as potential etiologies of autism. Recently we demonstrated that sera from children with autism alter the proliferation and neuronal maturation of human neuronal progenitor cells (hNPCs) in culture. Our study revealed that sera from children with autism immunoreact with neuronal progenitors in the dentate gyrus of the mouse hippocampus.

Objectives: To evaluate sera from children with autism for the presence of autoantibodies directed against human neuronal progenitors at distinct stages of maturation in culture.

Methods: The presence of antibodies against neuronal progenitors was tested in sera collected from control and affected siblings from 4 families, and in sera from unrelated control children (n=14) and children with autism (n=20) aged up to 5 years.  Reactions against proliferating hNPCs (day 0); and during neuronal maturation induced in culture (day 3 and day 7) were revealed by immunoblotting using sera diluted 1:250, and by immunocytochemistry using sera diluted 1:100. Cells immunoreactive to sera were identified by 3 color-immunofluorescence using markers of immature progenitors (Sox2, nestin), migrating progenitors (doublecortin), and mature cells (Tuj1, NeuN, GFAP).

Results: Sera from children up to 5 years of age contain antibodies that react with neuronal progenitors during neuronal maturation. As detected by the immunoblotting method, sera most frequently reacted with several proteins with molecular weight of 55 kD, 100-105 kD, 150-160 kD and 210-240 kD. Evident immunoreactivities with multiple bands were detected in 14% of control children and in 35% of children with autism. The intensity of this immunoreaction correlated with the stage of hNPCs maturation. The immunocytochemical method revealed a stronger immunoreaction against hNPCs in sera from children with autism than sera from unaffected siblings. The 3 color-immunofluorescence results suggest that antibodies in sera recognize a subpopulation of neuronal progenitors that express neuronal but not glial markers.

Conclusions: Sera from young children with autism contain antibodies that recognize several proteins of differentiating neuronal progenitors more frequently than controls. This suggests that autoimmune reactions may participate in alterations of early neuronal development. Elimination of specific antibodies against neuronal progenitors may represent a potential treatment strategy in autism.