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Lessons Learned from Targeting IGF-I Receptor in Thyroid-Associated Ophthalmopathy

Complex immunological mechanisms underlie the pathogenesis of thyroid-associated ophthalmopathy (TAO). Historical models of Graves’ disease and TAO have focused almost entirely on autoimmune reactivity directed against the thyrotropin receptor (TSHR). The insulin-like growth factor-I receptor (IGF-I...

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Autores principales: Janssen, Joseph A.M.J.L., Smith, Terry J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917650/
https://www.ncbi.nlm.nih.gov/pubmed/33673340
http://dx.doi.org/10.3390/cells10020383
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author Janssen, Joseph A.M.J.L.
Smith, Terry J.
author_facet Janssen, Joseph A.M.J.L.
Smith, Terry J.
author_sort Janssen, Joseph A.M.J.L.
collection PubMed
description Complex immunological mechanisms underlie the pathogenesis of thyroid-associated ophthalmopathy (TAO). Historical models of Graves’ disease and TAO have focused almost entirely on autoimmune reactivity directed against the thyrotropin receptor (TSHR). The insulin-like growth factor-I receptor (IGF-IR) has been proposed as a second participating antigen in TAO by virtue of its interactions with IGFs and anti-IGF-IR antibodies generated in Graves’ disease. Furthermore, the IGF-IR forms with TSHR a physical and functional complex which is involved in signaling downstream from both receptors. Inhibition of IGF-IR activity results in attenuation of signaling initiated at either receptor. Based on the aggregate of findings implicating IGF-IR in TAO, the receptor has become an attractive therapeutic target. Recently, teprotumumab, a human monoclonal antibody IGF-IR inhibitor was evaluated in two clinical trials of patients with moderate to severe, active TAO. Those studies revealed that teprotumumab was safe and highly effective in reducing disease activity and severity. Targeting IGF-IR with specific biologic agents may result in a paradigm shift in the therapy of TAO.
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spelling pubmed-79176502021-03-02 Lessons Learned from Targeting IGF-I Receptor in Thyroid-Associated Ophthalmopathy Janssen, Joseph A.M.J.L. Smith, Terry J. Cells Review Complex immunological mechanisms underlie the pathogenesis of thyroid-associated ophthalmopathy (TAO). Historical models of Graves’ disease and TAO have focused almost entirely on autoimmune reactivity directed against the thyrotropin receptor (TSHR). The insulin-like growth factor-I receptor (IGF-IR) has been proposed as a second participating antigen in TAO by virtue of its interactions with IGFs and anti-IGF-IR antibodies generated in Graves’ disease. Furthermore, the IGF-IR forms with TSHR a physical and functional complex which is involved in signaling downstream from both receptors. Inhibition of IGF-IR activity results in attenuation of signaling initiated at either receptor. Based on the aggregate of findings implicating IGF-IR in TAO, the receptor has become an attractive therapeutic target. Recently, teprotumumab, a human monoclonal antibody IGF-IR inhibitor was evaluated in two clinical trials of patients with moderate to severe, active TAO. Those studies revealed that teprotumumab was safe and highly effective in reducing disease activity and severity. Targeting IGF-IR with specific biologic agents may result in a paradigm shift in the therapy of TAO. MDPI 2021-02-12 /pmc/articles/PMC7917650/ /pubmed/33673340 http://dx.doi.org/10.3390/cells10020383 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Janssen, Joseph A.M.J.L.
Smith, Terry J.
Lessons Learned from Targeting IGF-I Receptor in Thyroid-Associated Ophthalmopathy
title Lessons Learned from Targeting IGF-I Receptor in Thyroid-Associated Ophthalmopathy
title_full Lessons Learned from Targeting IGF-I Receptor in Thyroid-Associated Ophthalmopathy
title_fullStr Lessons Learned from Targeting IGF-I Receptor in Thyroid-Associated Ophthalmopathy
title_full_unstemmed Lessons Learned from Targeting IGF-I Receptor in Thyroid-Associated Ophthalmopathy
title_short Lessons Learned from Targeting IGF-I Receptor in Thyroid-Associated Ophthalmopathy
title_sort lessons learned from targeting igf-i receptor in thyroid-associated ophthalmopathy
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917650/
https://www.ncbi.nlm.nih.gov/pubmed/33673340
http://dx.doi.org/10.3390/cells10020383
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