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Printable Handouts
Navigable Slide Index
- Introduction
- AITD
- Etiology of AITD - infection
- Epidemiological evidence
- Infection and AITD
- Molecular mimicry
- Bystander activation
- Etiology of AITD - iodine
- Iodine and AITD
- Iodine and AITD - mechanisms
- Etiology of AITD - stress
- Stress and Graves’ disease (GD)
- Etiology of AITD - smoking
- Smoking and AITD
- Smoking and AITD - summary
- Environmental risk factors for AITD
- Evidence for genetic susceptibility
- AITD cluster in families - Amsterdam cohort
- AITD cluster in families
- Genetic susceptibility to AITD
- Twin studies in AITD
- Methods for identifying complex disease genes
- Identifying susceptibility genes for diseases
- Gene susceptibility identification model
- Susceptibility genes identified in AITD
- Putative AITD susceptibility genes in Caucasians
- The immunological synapse
- HLA-DR in GD
- HLA associations in GD (caucasians)
- HLA-DR sequence variants association with GD
- Amino acid sequences of HLA-DR3 subtypes
- HLA-DR peptide binding groove
- Structure of the peptide binding groove
- Suggested mechanism
- HLA-DR summary
- The CTLA-4 gene in AITD (2q)
- Function of CTLA-5
- CTLA-4 studies in AITD (Caucasians)
- Which variant causes autoimmunity?
- These polymorphisms are in LD
- Functional studies
- Blocking CTLA-4 augments T-cell proliferation
- Genotype association with reduced CTLA-4
- Direct functional studies
- Causative polymorphism mapping
- CTLA-4 summary
- The CD40 gene in GD
- Function of CD40
- A new SNP in the Kozak sequence of CD40
- The CD40 Kozak SNP in GD
- Kozak sequences and translation
- Kozak SNP and CD40 translation
- In vitro transcription/translation assay for CD40
- CD40 surface expression on Rat2 cells
- CD40 expression on B cells
- FACS analysis of CD19+CD40+ purified B cells
- Higher cell surface expression of CD40
- Increased CD40 expression – where?
- Transgenic mice over-expressing CD40 on TFC
- Experimental autoimmune GD (EAGD)
- TRAb levels in EAGD mice
- Increase in T4 levels in EAGD mice
- CD40 expression induce or accelerate GD
- CD40 signaling pathways
- Canonical pathway activation
- Non-canonical pathway activation
- CD40 summary
- Development of AITD
Topics Covered
- Autoimmune thyroid diseases (AITD)
- Identification of AITD susceptibility genes
- Iodine and AITD
- MHC class II genes, CTLA-4, and CD40
- Sequencing efforts
- Environmental and genetic triggering factors of AITD
- Genetic studies and etiology of AITD
- Development of AITD
Links
Series:
Categories:
Therapeutic Areas:
Talk Citation
Tomer, Y. (2018, October 31). Genetic and environmental triggers of autoimmune thyroid diseases [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved November 21, 2024, from https://doi.org/10.69645/OFGO5628.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Yaron Tomer has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
A selection of talks on Immunology
Transcript
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0:00
The topic of my talk is
"Genetic and Environmental Triggers of Autoimmune Thyroid Diseases".
0:08
Autoimmune thyroid diseases are believed to develop as a result of
an interaction between genetic factors and environmental triggers.
This interaction leads to
the final disease phenotype which could be Graves' disease which manifests
clinically by hyperthyroidism or
Hashimoto's thyroiditis which manifests clinically by hypothyroidism.
0:34
I will first discuss the environmental triggers of autoimmune thyroid diseases.
I will discuss infection, iodine exposure, stress,
and smoking as triggers of autoimmune thyroid diseases.
I will start by discussing infection.
0:54
There is abundant epidemiological evidence for
an infectious trigger of autoimmune thyroid diseases.
For example, in one study from the United Kingdom,
there was seasonality in the presentation of Graves' disease with
more cases appearing in the summer than in other seasons.
In another study, there was evidence for
recent bacterial or viral infection in 36 percent of newly diagnosed Graves' patients.
And in a mouse model of Graves' disease,
it was found that mice bread in
a conventional facility where they are exposed to many infectious agents they developed
higher and more persistent levels of
TSH receptor antibodies compared to mice bread in a pathogen-free facility.