Brain-derived neurotrophic factor and autoantibodies to neural antigens in sera of children with autistic spectrum disorders, Landau-Kleffner syndrome, and epilepsy.
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 < or = 0.0002) compared to HC or NNI. Mean IgG and IgM BDNF AAs were elevated in children with autism, CDD and epilepsy (p < or = 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 < or = 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.


CONCLUSIONS
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.
Connolly
Anne M
AM
Department of Neurology and Pediatrics, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Chez
Michael
M
Streif
Elizabeth M
EM
Keeling
Richard M
RM
Golumbek
Paul T
PT
Kwon
Jennifer M
JM
Riviello
James J
JJ
Robinson
Ricki G
RG
Neuman
Rosalind J
RJ
Deuel
Ruth Mary K
RM
D000974:Antibodies, Antinuclear / Q000032:analysis; D001321:Autistic Disorder / Q000276:immunology* / Q000378:metabolism*; D001323:Autoantibodies / Q000032:analysis / Q000276:immunology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000276:immunology / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D042783:Endothelial Cells / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D004827:Epilepsy / Q000276:immunology*; D005260:Female; D006657:Histones / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis / Q000276:immunology; D007075:Immunoglobulin M / Q000032:analysis / Q000276:immunology; D007150:Immunohistochemistry; D018887:Landau-Kleffner Syndrome / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D004676:Myelin Basic Protein / Q000276:immunology / Q000378:metabolism; D009420:Nervous System / Q000276:immunology* / Q000378:metabolism*; D014471:Umbilical Veins / Q000166:cytology
D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D019208:Brain-Derived Neurotrophic Factor; D006657:Histones; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D004676:Myelin Basic Protein