Brain-Derived Neurotrophic Factor and Autoantibodies to Neural Antigens in Sera of Children with Autistic Spectrum Disorders, Landau-Kleffner Syndrome, and Epilepsy

Connolly, Anne M.; Chez, Michael; Streif, Elizabeth M.; Keeling, Richard M.; Golumbek, Paul T.; Kwon, Jennifer M.; Riviello, James J.; Robinson, Ricki G.; Neuman, Rosalind J.; Deuel, Ruth Mary K.

doi:10.1016/j.biopsych.2005.07.004

« Previous Next »Biological Psychiatry
Volume 59, Issue 4 , Pages 354-363, 15 February 2006

Brain-Derived Neurotrophic Factor and Autoantibodies to Neural Antigens in Sera of Children with Autistic Spectrum Disorders, Landau-Kleffner Syndrome, and Epilepsy

Anne M. Connolly
- Department of Neurology and Pediatrics, Washington University School of Medicine, St. Louis, Missouri
- Address reprint requests to Dr. Anne Connolly, Department of Neurology, Box 8111, Washington University School of Medicine, 660 S Euclid Ave, St. Louis, MO 63110
Michael Chez
- Department of Neurology, Rosalind Franklin University, Chicago Medical School, Chicago, Illinois
Elizabeth M. Streif
- Department of Neurology and Pediatrics, Washington University School of Medicine, St. Louis, Missouri
Richard M. Keeling
- Department of Neurology and Pediatrics, Washington University School of Medicine, St. Louis, Missouri
Paul T. Golumbek
- Department of Neurology and Pediatrics, Washington University School of Medicine, St. Louis, Missouri
Jennifer M. Kwon
- University of Rochester, Rochester, New York
James J. Riviello
- Harvard Medical School, Boston, Massachusetts
Ricki G. Robinson
- Keck School of Medicine at USC, Los Angeles, California
Rosalind J. Neuman
- Department of Psychiatry and Genetics, Washington University School of Medicine, St. Louis, Missouri
Ruth Mary K. Deuel
- Saint Louis University, St. Louis, Missouri

Received 19 January 2005; received in revised form 10 June 2005; accepted 1 July 2005. published online 23 September 2005.

Background

Brain derived neurotrophic factor (BDNF) elevation in newborn sera predicts intellectual/social developmental abnormalities. Other autoantibodies (AAs) to endothelial cells (ECs) and myelin basic protein (MBP) are also elevated in some children. We tested relationships between BDNF, BDNF AAs, and other AAs in children with these disorders.

Methods

BDNF levels and IgG/IgM autoantibodies to BDNF, ECs, MBP, and histones were measured in children with autism, childhood disintegrative disorder (CDD), pervasive developmental delay-not otherwise specified (PDD-nos), acquired epilepsy, Landau-Kleffner syndrome (LKS); healthy children (HC), and children with non-neurological illnesses (NNI).

Results

Mean BDNF levels were elevated in children with autism and CDD, (p ≤ 0.0002) compared to HC or NNI. Mean IgG and IgM BDNF AAs were elevated in children with autism, CDD and epilepsy (p ≤ 0.0005) compared to HC but not to NNI. Mean IgM AA EC titers detected by immunocytochemistry were higher in autism, PDD-NOS, epilepsy, and LKS (p ≤ 0.005) compared to HC and NNI. While mean ELISA IgG EC AAs were higher in autism and PPD-NOS (p < 0.005) compared to HC but not NNI, ELISA IgM EC AAs were higher in children with autism, CDD, PDD-NOS, and epilepsy compared to both HC and NNI (p < 0.0005). Mean anti-MBP IgG and IgM titers were higher in all study groups (p < 0.005) except for LKS compared to both HC and NNI.

Conclusion

Children with developmental disorders and epilepsy have higher AAs to several neural antigens compared to controls. The presence of both BDNF AAs and elevated BDNF levels in some children with autism and CDD suggests a previously unrecognized interaction between the immune system and BDNF.

Key Words: Antiendothelial antibodies , autoantibodies , antinuclear antibodies , Landau-Kleffner syndrome , autistic spectrum disorder