TY - JOUR
T1 - Brain-derived neurotrophic factor and autoantibodies to neural antigens in sera of children with autistic spectrum disorders, Landau-Kleffner syndrome, and epilepsy
AU - Connolly, Anne M.
AU - Chez, Michael
AU - Streif, Elizabeth M.
AU - Keeling, Richard M.
AU - Golumbek, Paul T.
AU - Kwon, Jennifer M.
AU - Riviello, James J.
AU - Robinson, Ricki G.
AU - Neuman, Rosalind J.
AU - Deuel, Ruth Mary K.
N1 - Funding Information:
This work was supported by a grant from the Hope Foundation to AMC.
PY - 2006/2/15
Y1 - 2006/2/15
N2 - 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.
AB - 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.
KW - Antiendothelial antibodies
KW - Antinuclear antibodies
KW - Autistic spectrum disorder
KW - Autoantibodies
KW - Landau-Kleffner syndrome
UR - http://www.scopus.com/inward/record.url?scp=32544434349&partnerID=8YFLogxK
U2 - 10.1016/j.biopsych.2005.07.004
DO - 10.1016/j.biopsych.2005.07.004
M3 - Article
C2 - 16181614
AN - SCOPUS:32544434349
SN - 0006-3223
VL - 59
SP - 354
EP - 363
JO - Biological Psychiatry
JF - Biological Psychiatry
IS - 4
ER -