Restricted tissue reactivity of autoantibodies to a 64-kDa eye muscle membrane antigen in thyroid-associated ophthalmopathy

Zhang, Z.-G.; Salvi, Mario; Miller, A.; Bernard, Nicole F.; Arthurs, Bryan; Wall, Jack R.

doi:10.1016/0090-1229(92)90071-u

Cited by 20 publications

(2 citation statements)

References 20 publications

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“…Os alvos desta resposta são principalmente os fibroblastos retro-bulbares existentes no intersticio dos músculos extra-oculares que se pensa apresentarem um fenótipo que os torna distintos 23,24 , bem como outros elementos dos tecidos da órbita, que por acção directa de células T ou imunomediada por citocinas são activados, proliferando, e diferenciando-se em adipócitos e produzindo mucopolissacarideos que conduzem ao edema secundário 25 . Foi identificada uma proteina de membrana de 64-Kda, que parece exclusiva da tiroideia e de fibroblastos orbitários [26][27][28] , segundo estudos recentes estará realcionada com subunidade flavoproteica da enzima mitocondrial succinato desidrogenase 29 . Num estudo publicado em 1995 30 detectaram-se titulos destes auto-anticorpos em 67 % de doentes com OAT, em 30% em doentes com D. Graves sem OAT marcada e só em 9% de individuos normais.…”

Section: Fisiopatologiaunclassified

Thyroid-Associated Ophthalmopathy

Feng

2019

Integrative Ophthalmology

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A oftalmopatia associada à tiroide, é uma situação relativamente rara, auto-limitada, que se caracteriza por um infiltrado inflamatório difuso da órbita, bilateral, assimétrico, condicionando exoftalmia e edema palpebral. Em 90% dos casos surge associada a D. Graves, mas por vezes também a hipotiroidismo ou eutiroidismo. Em cerca de 25% dos casos surge concomitantemente com a doença tiroideia, podendo no entanto precedêla ou sucedê-la com anos de intervalo. Cursa habitualmente com remissões e exacerbações espontâneas, evoluindo de forma independente relativamente à doença da tiroide, habitualmente sem gravidade para o doente, podendo apesar de tudo originar diplopia e cegueira em 1% dos casos. A causa é ainda pouco compreendida mas pensase que resulte duma alteração do sistema imunitário que permite a produção de autoanticorpos, cujos alvos são principalmente os fibroblastos retro-bulbares e tiroideia. A terapeutica é controversa, faltando ainda estabelecer com segurança um balanço entre os beneficios e os riscos da medicação. Palavras chave: oftalmopatia associada à tiroide; D. Graves; Revisão THYROID ASSOCIATED OPHTHALMOPATHY Thyroid associated ophthalmopathy is an uncommon disease, characterized by a diffuse inflammation of the orbit in a bilateral and assimetric pattern, causing proptosis and swelling of the eyelids and conjuntiva. In 90% of the patients it is associated with Graves' disease, however it may occur with hipothyroidism or even without thyroid disease. During its course spontaneous remission or exacerbations are common, evolving independently from the thyroid disease, most often without serious complications for the patient, being blindness the worse of them, in 1% of the cases. The cause is still misunderstood but it is thought to be the result of an immune system disorder with the production of auto-antibodies directed against retro-bulbar fibroblasts and thyroid. Therapeutics is still a controversial matter. The balance between benefits and medication adverse effects is still to be made.

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Section: Fisiopatologiaunclassified

Thyroid-Associated Ophthalmopathy

Feng

2019

Integrative Ophthalmology

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“…65 Thyroid-associated ophthalmology (exopthalmos) is an autoimmune inflammatory disorder of the periorbital muscles and connective tissue. More recently, various groups have reported reactivity to a 64-kD protein in human and porcine eye muscle in the serum of patients with ophthalmology 70,71 and this has been identified as a 67-kD flavoprotein subunit of the mitochondrial enzyme, succinate dehyrogenase 72 besides three additional protein targets for anti-eye muscle antibodies. TSH receptor autoantibodies may not be detected in some euthyroid patients with Graves' ophthalmopathy 67 and correlations with exopthalmos remain controversial.…”

Section: Thyroid Autoantibodiesmentioning

confidence: 99%

Autoimmune Endocrine Disorders

Ergun-Longmire¹,

Maclaren²

2016

Endocrinology: Adult and Pediatric

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Two dimensional gel electrophoresis identifies minor differences in immunologically cross-reactive 64 KDA autoantigens in the thyroid and eye muscle

Boucher

Bernard

Miller

et al. 1994

J Endocrinol Invest

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Among the candidate eye muscle autoantigens proposed as being relevant to the pathogenesis of thyroid-associated ophthalmopathy (TAO), a 64 kDa membrane autoantigen appears to be most closely associated with the eye disorder. We have examined the tissue localization and some of the physicochemical properties of this molecule in 3 human tissues, namely thyroid (THY), eye muscle (EM) and skeletal muscle (SKE), and in pig eye muscle (PEM), by two-dimensional (2-D) [isoelectric focusing (IEF)/sodium dodecyl polyacrylamide gel electrophoresis (SDS-PAGE)] gel electrophoresis followed by Western blotting. Antibody probes used were whole sera from patients with TAO and antibodies affinity purified from TAO sera by binding to, and elution from, a sepharose-4B column conjugated with D1, a 98 amino acid peptide fragment of a recombinant 64 kDa thyroid autoantigen. Soluble membrane proteins eluted from a slice of SDS-PAGE gel containing 60-70 kDa material was prepared from the four tissues and used as antigen for 2-D gel separation. The presence of a 64 kDa antigen in THY and EM recognized by sera from patients with TAO, but only rarely by those from normal individuals, was confirmed. Pretreatment of the eluted 60-70 kDa material with N-Glycosidase F to eliminate charge heterogeneity resulting from glycosylation differences, changed the pI and MW of molecules recognized by TAO sera, in THY and EM. This suggests that the 64 kDa molecule(s) in EM and THY targeted by sera from patients with TAO are glycoproteins and that they are different in the two tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

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Restricted tissue reactivity of autoantibodies to a 64-kDa eye muscle membrane antigen in thyroid-associated ophthalmopathy

Cited by 20 publications

References 20 publications

Thyroid-Associated Ophthalmopathy

Thyroid-Associated Ophthalmopathy

Autoimmune Endocrine Disorders

Two dimensional gel electrophoresis identifies minor differences in immunologically cross-reactive 64 KDA autoantigens in the thyroid and eye muscle

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