Pathogenesis of thyroid-associated ophthalmopathy: does autoimmunity against calsequestrin and collagen XIII play a role?

Hooshang Lahooti, Kishan R Parmar, Jack R WallThe Department of Medicine, University of Sydney, Nepean Clinical School, Penrith, NSW, AustraliaAbstract: Thyroid-associated ophthalmopathy (TAO), or thyroid eye disease, is a complex inflammatory disorder of the eye that, as its name implies, is associ...

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Autores principales:	Hooshang Lahooti, Kishan R Parmar, Jack R Wall
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2010
Materias:	Ophthalmology RE1-994
Acceso en línea:	https://doaj.org/article/706cc93bed3d473282fce83ad0e1e58e
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spelling	oai:doaj.org-article:706cc93bed3d473282fce83ad0e1e58e2021-12-02T00:49:23ZPathogenesis of thyroid-associated ophthalmopathy: does autoimmunity against calsequestrin and collagen XIII play a role?1177-54671177-5483https://doaj.org/article/706cc93bed3d473282fce83ad0e1e58e2010-04-01T00:00:00Zhttp://www.dovepress.com/pathogenesis-of-thyroid-associated-ophthalmopathy-does-autoimmunity-ag-a4343https://doaj.org/toc/1177-5467https://doaj.org/toc/1177-5483Hooshang Lahooti, Kishan R Parmar, Jack R WallThe Department of Medicine, University of Sydney, Nepean Clinical School, Penrith, NSW, AustraliaAbstract: Thyroid-associated ophthalmopathy (TAO), or thyroid eye disease, is a complex inflammatory disorder of the eye that, as its name implies, is associated with thyroid disease. TAO can be divided into three subtypes: ocular myopathy, congestive myopathy and mixed congestive and myopathic ophthalmopathy. Although the precise pathophysiology of TAO remains unclear it is likely to reflect an autoimmune reaction involving sensitized T-cells and autoantibodies directed against a thyroid and orbital tissue shared antigen. One well studied candidate in this immune reaction is the thyroid-stimulating hormone receptor (TSH-r), expressed in the orbital fibroblast and pre adipocyte. In our studies of TAO, we have investigated the nature and significance of antibodies targeting other eye muscle and orbital connective tissue (OCT) antigens. Our findings suggest that autoimmunity against the eye muscle antigen calsequestrin and the OCT antigen collagen XIII plays a role in the pathogenesis of TAO. We propose that ocular myopathy and chronic eyelid retraction are due to autoimmunity against skeletal muscle calsequestrin in the extraocular and eyelid muscles, respectively. This may be initiated in the thyroid where calsequestrin expression is upregulated, possibly due to a stimulatory effect of TSH-r antibodies. We also propose that congestive ophthalmopathy results from a reaction against the TSH-r or collagen XIII in orbital fibroblast cell membranes. Further insight into the role of eye muscle and OCT antigens in the pathogenesis of TAO may allow for the development of new therapies to treat the eye disorder and reduce patient morbidity.Keywords: thyroid-associated ophthalmopathy, autoimmunity, t calsequestrin, collagen XIII Hooshang LahootiKishan R ParmarJack R WallDove Medical PressarticleOphthalmologyRE1-994ENClinical Ophthalmology, Vol 2010, Iss default, Pp 417-425 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Ophthalmology RE1-994
spellingShingle	Ophthalmology RE1-994 Hooshang Lahooti Kishan R Parmar Jack R Wall Pathogenesis of thyroid-associated ophthalmopathy: does autoimmunity against calsequestrin and collagen XIII play a role?
description	Hooshang Lahooti, Kishan R Parmar, Jack R WallThe Department of Medicine, University of Sydney, Nepean Clinical School, Penrith, NSW, AustraliaAbstract: Thyroid-associated ophthalmopathy (TAO), or thyroid eye disease, is a complex inflammatory disorder of the eye that, as its name implies, is associated with thyroid disease. TAO can be divided into three subtypes: ocular myopathy, congestive myopathy and mixed congestive and myopathic ophthalmopathy. Although the precise pathophysiology of TAO remains unclear it is likely to reflect an autoimmune reaction involving sensitized T-cells and autoantibodies directed against a thyroid and orbital tissue shared antigen. One well studied candidate in this immune reaction is the thyroid-stimulating hormone receptor (TSH-r), expressed in the orbital fibroblast and pre adipocyte. In our studies of TAO, we have investigated the nature and significance of antibodies targeting other eye muscle and orbital connective tissue (OCT) antigens. Our findings suggest that autoimmunity against the eye muscle antigen calsequestrin and the OCT antigen collagen XIII plays a role in the pathogenesis of TAO. We propose that ocular myopathy and chronic eyelid retraction are due to autoimmunity against skeletal muscle calsequestrin in the extraocular and eyelid muscles, respectively. This may be initiated in the thyroid where calsequestrin expression is upregulated, possibly due to a stimulatory effect of TSH-r antibodies. We also propose that congestive ophthalmopathy results from a reaction against the TSH-r or collagen XIII in orbital fibroblast cell membranes. Further insight into the role of eye muscle and OCT antigens in the pathogenesis of TAO may allow for the development of new therapies to treat the eye disorder and reduce patient morbidity.Keywords: thyroid-associated ophthalmopathy, autoimmunity, t calsequestrin, collagen XIII
format	article
author	Hooshang Lahooti Kishan R Parmar Jack R Wall
author_facet	Hooshang Lahooti Kishan R Parmar Jack R Wall
author_sort	Hooshang Lahooti
title	Pathogenesis of thyroid-associated ophthalmopathy: does autoimmunity against calsequestrin and collagen XIII play a role?
title_short	Pathogenesis of thyroid-associated ophthalmopathy: does autoimmunity against calsequestrin and collagen XIII play a role?
title_full	Pathogenesis of thyroid-associated ophthalmopathy: does autoimmunity against calsequestrin and collagen XIII play a role?
title_fullStr	Pathogenesis of thyroid-associated ophthalmopathy: does autoimmunity against calsequestrin and collagen XIII play a role?
title_full_unstemmed	Pathogenesis of thyroid-associated ophthalmopathy: does autoimmunity against calsequestrin and collagen XIII play a role?
title_sort	pathogenesis of thyroid-associated ophthalmopathy: does autoimmunity against calsequestrin and collagen xiii play a role?
publisher	Dove Medical Press
publishDate	2010
url	https://doaj.org/article/706cc93bed3d473282fce83ad0e1e58e
work_keys_str_mv	AT hooshanglahooti pathogenesisofthyroidassociatedophthalmopathydoesautoimmunityagainstcalsequestrinandcollagenxiiiplayarole AT kishanrparmar pathogenesisofthyroidassociatedophthalmopathydoesautoimmunityagainstcalsequestrinandcollagenxiiiplayarole AT jackrwall pathogenesisofthyroidassociatedophthalmopathydoesautoimmunityagainstcalsequestrinandcollagenxiiiplayarole
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Pathogenesis of thyroid-associated ophthalmopathy: does autoimmunity against calsequestrin and collagen XIII play a role?

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