Follow up of Brain Endothelial Antibodies in Children with Language Regression

Background: A high frequency of brain endothelial antibodies (BEA) has been observed in children with language regression (LR). The persistence of these antibodies on repeated measurements is unknown.

Objectives: Describe serial measurements of serum BAE in children with LR. Methods: We measured repeat serum BEA IgM (primary) and IgG (secondary) titers in 7 children with LR whose initial BEA titers were positive. Samples were analyzed at Dr Connolly s laboratory at Washington University.
Subjects were children with LR with (n=6) and without (n=1) autism recruited from the Albert Einstein College of Medicine hospital affiliates.  All had a documented language regression (loss of 5 previously acquired words). Mean age at regression in those with autism was 24.6 months. The child with isolated LR was 67 months and presented with seizures. All 7 were boys.Results: Initial blood samples showed positive IgM BAE titers in all 7 children and IgG titers in 3 (2 with autism and LR and one with LR only). Mean age at first BAE titer was 74 months (range 38-154).  Follow-up titers were obtained a mean of 24 months after the initial titer (range 11-43 months). Follow-up BEA titers were positive for IgM in all 7 children but only one child had positive IgG titers.  That child had LR and autism.
Conclusions: BAE serum antibodies are persistent. Interestingly, IgM antibodies that are usually the primary response are present years after the regression and persist on repeat testing. In contrast, IgG antibodies that are usually a secondary response are inconsistently present and when present on one sample, may not persist.  Continued immune reactivity as evidenced by persistent BAE IgM titers suggests the possibility of treatment with immune modulating agents even after the regression has already taken place.