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Graves’ orbitopathy occurs sex-independently in an autoimmune hyperthyroid mouse model

Graves’ orbitopathy (GO) is the most common extra thyroidal complication of Graves’ disease (GD) and occurs predominantly in women but more severe in men. The reason for this effect of gender on GO is unknown. Herein we studied the manifestation of GO in both sexes of an induced mouse model in absen...

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Autores principales: Schlüter, Anke, Flögel, Ulrich, Diaz-Cano, Salvador, Görtz, Gina-Eva, Stähr, Kerstin, Oeverhaus, Michael, Plöhn, Svenja, Mattheis, Stefan, Moeller, Lars C., Lang, Stephan, Bechrakis, Nikolaos E., Banga, J. Paul, Eckstein, Anja, Berchner-Pfannschmidt, Utta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6117361/
https://www.ncbi.nlm.nih.gov/pubmed/30166557
http://dx.doi.org/10.1038/s41598-018-31253-4
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author Schlüter, Anke
Flögel, Ulrich
Diaz-Cano, Salvador
Görtz, Gina-Eva
Stähr, Kerstin
Oeverhaus, Michael
Plöhn, Svenja
Mattheis, Stefan
Moeller, Lars C.
Lang, Stephan
Bechrakis, Nikolaos E.
Banga, J. Paul
Eckstein, Anja
Berchner-Pfannschmidt, Utta
author_facet Schlüter, Anke
Flögel, Ulrich
Diaz-Cano, Salvador
Görtz, Gina-Eva
Stähr, Kerstin
Oeverhaus, Michael
Plöhn, Svenja
Mattheis, Stefan
Moeller, Lars C.
Lang, Stephan
Bechrakis, Nikolaos E.
Banga, J. Paul
Eckstein, Anja
Berchner-Pfannschmidt, Utta
author_sort Schlüter, Anke
collection PubMed
description Graves’ orbitopathy (GO) is the most common extra thyroidal complication of Graves’ disease (GD) and occurs predominantly in women but more severe in men. The reason for this effect of gender on GO is unknown. Herein we studied the manifestation of GO in both sexes of an induced mouse model in absence of additional risk factors present in patients like advanced age, genetic variabilities or smoking. Male and female mice were immunized with human TSHR A-subunit encoding plasmid. Both sexes comparably developed autoimmune hyperthyroidism characterized by TSHR stimulating autoantibodies, elevated T4 values, hyperplastic thyroids and hearts. Autoimmune mice developed inflammatory eye symptoms and proptosis, although males earlier than females. Serial in vivo (1)H/(19)F-magnetic resonance imaging revealed elevated inflammatory infiltration, increased fat volume and glycosaminoglycan deposition in orbits of both sexes but most significantly in female mice. Histologically, infiltration of T-cells, extension of brown fat and overall collagen deposition were characteristics of GO in male mice. In contrast, female mice developed predominately macrophage infiltration in muscle and connective tissue, and muscle hypertrophy. Apart from sex-dependent variabilities in pathogenesis, disease classification revealed minor sex-differences in incidence and total outcome. In conclusion, sex does not predispose for autoimmune hyperthyroidism and associated GO.
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spelling pubmed-61173612018-09-05 Graves’ orbitopathy occurs sex-independently in an autoimmune hyperthyroid mouse model Schlüter, Anke Flögel, Ulrich Diaz-Cano, Salvador Görtz, Gina-Eva Stähr, Kerstin Oeverhaus, Michael Plöhn, Svenja Mattheis, Stefan Moeller, Lars C. Lang, Stephan Bechrakis, Nikolaos E. Banga, J. Paul Eckstein, Anja Berchner-Pfannschmidt, Utta Sci Rep Article Graves’ orbitopathy (GO) is the most common extra thyroidal complication of Graves’ disease (GD) and occurs predominantly in women but more severe in men. The reason for this effect of gender on GO is unknown. Herein we studied the manifestation of GO in both sexes of an induced mouse model in absence of additional risk factors present in patients like advanced age, genetic variabilities or smoking. Male and female mice were immunized with human TSHR A-subunit encoding plasmid. Both sexes comparably developed autoimmune hyperthyroidism characterized by TSHR stimulating autoantibodies, elevated T4 values, hyperplastic thyroids and hearts. Autoimmune mice developed inflammatory eye symptoms and proptosis, although males earlier than females. Serial in vivo (1)H/(19)F-magnetic resonance imaging revealed elevated inflammatory infiltration, increased fat volume and glycosaminoglycan deposition in orbits of both sexes but most significantly in female mice. Histologically, infiltration of T-cells, extension of brown fat and overall collagen deposition were characteristics of GO in male mice. In contrast, female mice developed predominately macrophage infiltration in muscle and connective tissue, and muscle hypertrophy. Apart from sex-dependent variabilities in pathogenesis, disease classification revealed minor sex-differences in incidence and total outcome. In conclusion, sex does not predispose for autoimmune hyperthyroidism and associated GO. Nature Publishing Group UK 2018-08-30 /pmc/articles/PMC6117361/ /pubmed/30166557 http://dx.doi.org/10.1038/s41598-018-31253-4 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Schlüter, Anke
Flögel, Ulrich
Diaz-Cano, Salvador
Görtz, Gina-Eva
Stähr, Kerstin
Oeverhaus, Michael
Plöhn, Svenja
Mattheis, Stefan
Moeller, Lars C.
Lang, Stephan
Bechrakis, Nikolaos E.
Banga, J. Paul
Eckstein, Anja
Berchner-Pfannschmidt, Utta
Graves’ orbitopathy occurs sex-independently in an autoimmune hyperthyroid mouse model
title Graves’ orbitopathy occurs sex-independently in an autoimmune hyperthyroid mouse model
title_full Graves’ orbitopathy occurs sex-independently in an autoimmune hyperthyroid mouse model
title_fullStr Graves’ orbitopathy occurs sex-independently in an autoimmune hyperthyroid mouse model
title_full_unstemmed Graves’ orbitopathy occurs sex-independently in an autoimmune hyperthyroid mouse model
title_short Graves’ orbitopathy occurs sex-independently in an autoimmune hyperthyroid mouse model
title_sort graves’ orbitopathy occurs sex-independently in an autoimmune hyperthyroid mouse model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6117361/
https://www.ncbi.nlm.nih.gov/pubmed/30166557
http://dx.doi.org/10.1038/s41598-018-31253-4
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