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Is There Evidence for IGF1R-Stimulating Abs in Graves’ Orbitopathy Pathogenesis?

In this review, we summarize the evidence against direct stimulation of insulin-like growth factor 1 receptors (IGF1Rs) by autoantibodies in Graves’ orbitopathy (GO) pathogenesis. We describe a model of thyroid-stimulating hormone (TSH) receptor (TSHR)/IGF1R crosstalk and present evidence that obser...

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Autores principales: Krieger, Christine C., Neumann, Susanne, Gershengorn, Marvin C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555308/
https://www.ncbi.nlm.nih.gov/pubmed/32911689
http://dx.doi.org/10.3390/ijms21186561
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author Krieger, Christine C.
Neumann, Susanne
Gershengorn, Marvin C.
author_facet Krieger, Christine C.
Neumann, Susanne
Gershengorn, Marvin C.
author_sort Krieger, Christine C.
collection PubMed
description In this review, we summarize the evidence against direct stimulation of insulin-like growth factor 1 receptors (IGF1Rs) by autoantibodies in Graves’ orbitopathy (GO) pathogenesis. We describe a model of thyroid-stimulating hormone (TSH) receptor (TSHR)/IGF1R crosstalk and present evidence that observations indicating IGF1R’s role in GO could be explained by this mechanism. We evaluate the evidence for and against IGF1R as a direct target of stimulating IGF1R antibodies (IGF1RAbs) and conclude that GO pathogenesis does not involve directly stimulating IGF1RAbs. We further conclude that the preponderance of evidence supports TSHR as the direct and only target of stimulating autoantibodies in GO and maintain that the TSHR should remain a major target for further development of a medical therapy for GO in concert with drugs that target TSHR/IGF1R crosstalk.
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spelling pubmed-75553082020-10-19 Is There Evidence for IGF1R-Stimulating Abs in Graves’ Orbitopathy Pathogenesis? Krieger, Christine C. Neumann, Susanne Gershengorn, Marvin C. Int J Mol Sci Review In this review, we summarize the evidence against direct stimulation of insulin-like growth factor 1 receptors (IGF1Rs) by autoantibodies in Graves’ orbitopathy (GO) pathogenesis. We describe a model of thyroid-stimulating hormone (TSH) receptor (TSHR)/IGF1R crosstalk and present evidence that observations indicating IGF1R’s role in GO could be explained by this mechanism. We evaluate the evidence for and against IGF1R as a direct target of stimulating IGF1R antibodies (IGF1RAbs) and conclude that GO pathogenesis does not involve directly stimulating IGF1RAbs. We further conclude that the preponderance of evidence supports TSHR as the direct and only target of stimulating autoantibodies in GO and maintain that the TSHR should remain a major target for further development of a medical therapy for GO in concert with drugs that target TSHR/IGF1R crosstalk. MDPI 2020-09-08 /pmc/articles/PMC7555308/ /pubmed/32911689 http://dx.doi.org/10.3390/ijms21186561 Text en © 2020 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
Krieger, Christine C.
Neumann, Susanne
Gershengorn, Marvin C.
Is There Evidence for IGF1R-Stimulating Abs in Graves’ Orbitopathy Pathogenesis?
title Is There Evidence for IGF1R-Stimulating Abs in Graves’ Orbitopathy Pathogenesis?
title_full Is There Evidence for IGF1R-Stimulating Abs in Graves’ Orbitopathy Pathogenesis?
title_fullStr Is There Evidence for IGF1R-Stimulating Abs in Graves’ Orbitopathy Pathogenesis?
title_full_unstemmed Is There Evidence for IGF1R-Stimulating Abs in Graves’ Orbitopathy Pathogenesis?
title_short Is There Evidence for IGF1R-Stimulating Abs in Graves’ Orbitopathy Pathogenesis?
title_sort is there evidence for igf1r-stimulating abs in graves’ orbitopathy pathogenesis?
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555308/
https://www.ncbi.nlm.nih.gov/pubmed/32911689
http://dx.doi.org/10.3390/ijms21186561
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