Maternal mid-pregnancy autoantibodies to fetal brain protein: the early markers for autism study

Abstract

Background: Immune dysfunction has been associated with autism, yet whether maternal immune status during pregnancy plays a causal role remains to be clarified.

Methods: We conducted a population-based case-control study nested within the cohort of infants born July 2000-September 2001 to women who participated in the prenatal screening program in Orange County, California. Cases (AU; n = 84) were children receiving services for autism at the Regional Center of Orange County. Two control groups were included: children with mental retardation or developmental delay (MR; n = 49) receiving services at the same regional center; and children not receiving services for developmental disabilities, randomly sampled from the California birth certificate files (GP; n = 160). Maternal autoantibody reactivity to fetal brain protein was measured by Western blot in archived mid-pregnancy blood specimens drawn during routine prenatal screening. Presence of specific bands and band patterns were compared between the three study groups.

Results: The pattern of maternal mid-gestation antibody reactivity to human fetal brain protein varied by study group and by autism onset type, although most differences did not reach statistical significance. Reactivity to a band at 39 kDa was more common among mothers of children with autism (7%) compared with mothers of MR (0%; p = .09) and GP control subjects (2%; p = .07), and simultaneous reactivity to bands at 39 kDa and 73 kDa was found only in mothers of children with early onset autism (n = 3).

Conclusions: Our findings indicate that further studies of prenatal immune markers might be a productive area for etiologic and biologic marker discovery for autism.

Figure 1

Representative lanes from western blot analysis of human fetal brain probed with serum from mothers of children with autism and those whose children are typically developing. Lane A represents a mother of a child with autism with the early onset phenotype with the 39-kDa:73-kDa band pattern. Lane B represents a mother of a child with regressive autism and the 37-kDa:73-kDa band pattern. Lane C represents a mother of a typically developing control child with no reactivity to fetal brain. The IgG heavy and light chains present in the fetal brain preparation are recognized by the secondary control and used as a reference marker.