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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| Format: | Article |
| Language: | English |
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MDPI AG
2021-02-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/10/2/383 |
| _version_ | 1797396751411314688 |
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| author | Joseph A.M.J.L. Janssen Terry J. Smith |
| author_facet | Joseph A.M.J.L. Janssen Terry J. Smith |
| author_sort | Joseph A.M.J.L. Janssen |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-09T00:56:10Z |
| format | Article |
| id | doaj.art-ff34779774784e98987f5bdc49a2c0ca |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T00:56:10Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-ff34779774784e98987f5bdc49a2c0ca2023-12-11T16:55:13ZengMDPI AGCells2073-44092021-02-0110238310.3390/cells10020383Lessons Learned from Targeting IGF-I Receptor in Thyroid-Associated OphthalmopathyJoseph A.M.J.L. Janssen0Terry J. Smith1Erasmus Medical Center, Department of Internal Medicine, Dr. Molewaterplein 40, 3015 GD Rotterdam, The NetherlandsKellogg Eye Center, Department of Ophthalmology and Visual Sciences, University of Michigan Medical School, Ann Arbor, MI 48105, USAComplex 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.https://www.mdpi.com/2073-4409/10/2/383Graves’ diseasethyroid-associated ophthalmopathyproptosisIGF-IRIGF-IR inhibitorsT cells |
| spellingShingle | Joseph A.M.J.L. Janssen Terry J. Smith Lessons Learned from Targeting IGF-I Receptor in Thyroid-Associated Ophthalmopathy Cells Graves’ disease thyroid-associated ophthalmopathy proptosis IGF-IR IGF-IR inhibitors T cells |
| 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 | Graves’ disease thyroid-associated ophthalmopathy proptosis IGF-IR IGF-IR inhibitors T cells |
| url | https://www.mdpi.com/2073-4409/10/2/383 |
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