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Brain-derived neurotrophic factor and autoantibodies to neural antigens in sera of children with autistic spectrum disorders, Landau-Kleffner syndrome, and epilepsy

Connolly AM, Chez M, Streif EM +7 more2006Biological PsychiatryJournal Article
10.1016/j.biopsych.2005.07.004PubMed
Immune/InnateNeurological

Abstract

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. 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 Biomarkers

Autoantibodies to endothelial cellsAutoantibodies to histonesAutoantibodies to myelin basic proteinBDNF (Brain-derived neurotrophic factor)IgG autoantibodies to BDNFIgM autoantibodies to BDNF

Symptom Clusters

Autism spectrum disordersChildhood disintegrative disorderEpilepsyLandau-Kleffner syndromePervasive developmental delay

References (3)

  • Serum autoantibodies to brain in Landau-Kleffner Variant, autism, and other neurologic disordersThe Journal of Pediatrics · 1999
  • Serological association of measles virus and human herpesvirus-6 with brain autoantibodies in autismClinical Immunology and Immunopathology · 1998
  • Antibodies to myelin basic protein in children with autistic behaviorBrain Behavior and Immunity · 1993

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