TY - JOUR
T1 - Genetics and epigenetics of autoimmune thyroid diseases
T2 - Translational implications
AU - Lee, Hanna J.
AU - Stefan–Lifshitz, Mihaela
AU - Li, Cheuk Wun
AU - Tomer, Yaron
N1 - Funding Information:
This work was supported in part by grants DK067555 and DK073681 from NIDDK (to YT) and by a research grant from the American Thyroid Association (to CWL).
Funding Information:
Dr. Tomer declares that he was previously (1/2015–6/2017) the principal investigator on a basic research project jointly funded by the Juvenile Diabetes Research Foundation and Pfizer. The current manuscript is not related to that research project. Drs. Tomer and Li declare that they submitted a patent application for Cepharanthine as a treatment for APS3v and T1D. Dr. Tomer also declares that he submitted patent applications for Cepharanthine as a treatment for AITD, for a method for predicting patient response to CD40-targeted therapies, and for peptide treatment for T1D. All other authors have no potential conflict of interest to declare. Practice points Research agenda
Publisher Copyright:
© 2022 Elsevier Ltd
PY - 2022
Y1 - 2022
N2 - Hashimoto's thyroiditis (HT) and Graves' disease (GD) are prevalent autoimmune disorders, representing opposite ends of the clinical spectrum of autoimmune thyroid diseases (AITD). The pathogenesis involves a complex interplay between environment and genes. Specific susceptibility genes have been discovered that predispose to AITD, including thyroid-specific and immune-regulatory genes. Growing evidence has revealed that genetic and epigenetic variants can alter autoantigen presentation during the development of immune tolerance, can enhance self-peptide binding to MHC (major histocompatibility complex), and can amplify stimulation of T- and B-cells. These gene-driven mechanistic discoveries lay the groundwork for novel treatment targets. This review summarizes recent advances in our understanding of key AITD susceptibility genes (Tg1, TSHR, HLA-DR3, and CD40) and their translational therapeutic potential.
AB - Hashimoto's thyroiditis (HT) and Graves' disease (GD) are prevalent autoimmune disorders, representing opposite ends of the clinical spectrum of autoimmune thyroid diseases (AITD). The pathogenesis involves a complex interplay between environment and genes. Specific susceptibility genes have been discovered that predispose to AITD, including thyroid-specific and immune-regulatory genes. Growing evidence has revealed that genetic and epigenetic variants can alter autoantigen presentation during the development of immune tolerance, can enhance self-peptide binding to MHC (major histocompatibility complex), and can amplify stimulation of T- and B-cells. These gene-driven mechanistic discoveries lay the groundwork for novel treatment targets. This review summarizes recent advances in our understanding of key AITD susceptibility genes (Tg1, TSHR, HLA-DR3, and CD40) and their translational therapeutic potential.
KW - CD40
KW - HLA
KW - TSHR
KW - autoimmune thyroid disease
KW - genes
KW - thyroglobulin
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U2 - 10.1016/j.beem.2022.101661
DO - 10.1016/j.beem.2022.101661
M3 - Review article
AN - SCOPUS:85128677464
JO - Best Practice and Research in Clinical Endocrinology and Metabolism
JF - Best Practice and Research in Clinical Endocrinology and Metabolism
SN - 1521-690X
M1 - 101661
ER -
