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Autism & Autoimunty

Britt van Hagen & Róbert Zimmeramnn
by

Róbert Zimmermann

on 14 May 2013

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Transcript of Autism & Autoimunty

Autism & Autoimmunity Overview Introduction Autism spectrum disorder (ASD) symptoms pathophysiology Maternal (paternal) autoimmunity Proposed mechanism Signaling pathway Inflammatory cytokines & chemokines Immune dysfunction in ASD patients Genes Transfer from F1 to F2 Thank you for your attention.

If you have some questions do not hesitate and ask please. Summary Developmental disabilities in:
Speech and communication
Social interest and interaction
Stereotypic behavior or mannerisms Brain enlargement or reduction in different areas
Problems with mirror neuron system (empathy)
Temporal lobe: fusiform face area
Enlarged ventricles
Altered serotonergic and dopaminergic pathways Family studies showed association of autoimmune dysfunction & autistic offspring Auto-antibodies, directed against neuronal components of fetal brain, are found in 12% of ASD children's mothers Quality vs quantity
HLA gene, HLA-DR4
ASD F2 shares more often haplotype of HLA with F1xx
MIF, MET, PRKCB, PTEN, FMRP, RELN, Hoxa1, SLC25A
GABA r, oxitocin, vazopresin
several microsatellite linkages within the MHC were associated with ASD ASD patients show elevated levels of inflammatory cytokines in the CNS
IL-6, TNF-alpha, and MCP-1
in brain specimens and CSF
NF-kB upregulated in blood
and brain tissue
Suggests active neuro-
inflammatory process immune activation causing inflammation has detrimental effects on CNS tissue
decreased number of T-lymphocytes & altered responses
reduced number of NK cells
monocytes from ASD patients show increases or decreases in pro-inflammatory cytokines depending on TLR ligand Antibodies in ASD patients antibodies directed against adult brain or CNS tissue found
serum antibodies positively correlate to severity of autistic symptoms In some cases autism seems to be related to autoimmunity of the parents
Many immune related genes are associated with ASD
Auto-antibodies can cause damage to neuronal tissue, leading to ASD symptoms
A possible mechanism, leading to autism, is that maternal pro-inflammatory cytokines cause life-long changes in the fetal brain to disease relevant structures Introduction
Maternal/Paternal autoimmunity
Antibody transfer hypothesis
Immune related genes and ASD
Immunity in ASD patients
Antibodies in ASD patients
Signal transduction pathway
Proposed mechanism
Summary Britt van Hagen & Róbert Zimmermann (huntingtin, FMR1) Hints for discussion or just for thinking Why is pregnant woman in risk of developing autoimmunal disease (and therefore offspring in develpment of autism)?
What is reason for savatism? Elevated levels of proinflamatory cytokines induce activation of microglia & astrocytes. Activated astrocytes & microglia are releasing more NGF than usually. Higher density of neurons. Higher levels of TNF-alpha = higher plasticity and connectivity between neurons.
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