Amino acid sequence homology between thyroid autoantigens and central nervous system proteins: Implications for the steroid-responsive encephalopathy associated with autoimmune thyroiditis

A few patients with Hashimoto’s thyroiditis or Graves’ disease develop a multiform syndrome of the central nervous system (CNS) termed Hashimoto’s encephalopathy or steroid-responsive encephalopathy associated with autoimmune thyroid disease (HE/SREAT). They have high levels of thyroid autoantibodie...

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Autores principales:	Salvatore Benvenga, Alessandro Antonelli, Poupak Fallahi, Carmen Bonanno, Carmelo Rodolico, Fabrizio Guarneri
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Graves’ disease Hashimoto’s encephalopathy Thyroglobulin Thyroperoxidase Thyrotropin receptors Bioinformatics Diseases of the endocrine glands. Clinical endocrinology RC648-665
Acceso en línea:	https://doaj.org/article/502aeba0361445e3a55e14e58d70cb5d
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spelling	oai:doaj.org-article:502aeba0361445e3a55e14e58d70cb5d2021-11-22T04:25:53ZAmino acid sequence homology between thyroid autoantigens and central nervous system proteins: Implications for the steroid-responsive encephalopathy associated with autoimmune thyroiditis2214-623710.1016/j.jcte.2021.100274https://doaj.org/article/502aeba0361445e3a55e14e58d70cb5d2021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2214623721000260https://doaj.org/toc/2214-6237A few patients with Hashimoto’s thyroiditis or Graves’ disease develop a multiform syndrome of the central nervous system (CNS) termed Hashimoto’s encephalopathy or steroid-responsive encephalopathy associated with autoimmune thyroid disease (HE/SREAT). They have high levels of thyroid autoantibodies (TgAb, TPOAb and/or TSH-R-Ab) in blood and cerebrospinal fluid. Autoantibodies against alpha-enolase, aldehyde reductase-I (AKRIA) and/or dimethylargininase-I (DDAHI), proteins expressed in the CNS among other tissues, were detected in the blood and, when searched, in the cerebrospinal fluid of HE/SREAT patients. Recently, we reported that alpha-enolase, AKRIA and DDAHI share local sequence homology with each of the three autoantigens (TgAb, TPOAb, TSH-R-Ab), often in epitope-containing segments of the thyroid autoantigens. We hypothesized that there might be additional CNS-expressed proteins homologous to thyroid autoantigens, possibly overlapping known epitopes of the thyroid autoantigens. We used bioinformatic methods to address this hypothesis.Six, 27 and 47 of 46,809 CNS-expressed proteins share homology with TSH-R, Tg and TPO, respectively. The homologous regions often contain epitopes, and some match regions of thyroid autoantigens which have homology with alpha-enolase, AKRIA and/or DDAHI. Several of the aforementioned proteins are present in CNS areas that show abnormalities at neuroimaging in HE/SREAT patients. Furthermore, autoantibodies against some of the said six, 27 and 47 proteins were reported to be associated with a number of autoimmune diseases.Not only we validated our hypothesis, but we think that such a variety of potential CNS targets for thyroid Ab against epitopes contained in regions that have local homology with CNS proteins may explain the polymorphic phenotypes of HE/SREAT. Only when elevated amounts of these Ab are synthesized and trespass the blood-brain barrier, HE/SREAT appears. This might explain why HE/SREAT is so relatively rare.Salvatore BenvengaAlessandro AntonelliPoupak FallahiCarmen BonannoCarmelo RodolicoFabrizio GuarneriElsevierarticleGraves’ diseaseHashimoto’s encephalopathyThyroglobulinThyroperoxidaseThyrotropin receptorsBioinformaticsDiseases of the endocrine glands. Clinical endocrinologyRC648-665ENJournal of Clinical & Translational Endocrinology, Vol 26, Iss , Pp 100274- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Graves’ disease Hashimoto’s encephalopathy Thyroglobulin Thyroperoxidase Thyrotropin receptors Bioinformatics Diseases of the endocrine glands. Clinical endocrinology RC648-665
spellingShingle	Graves’ disease Hashimoto’s encephalopathy Thyroglobulin Thyroperoxidase Thyrotropin receptors Bioinformatics Diseases of the endocrine glands. Clinical endocrinology RC648-665 Salvatore Benvenga Alessandro Antonelli Poupak Fallahi Carmen Bonanno Carmelo Rodolico Fabrizio Guarneri Amino acid sequence homology between thyroid autoantigens and central nervous system proteins: Implications for the steroid-responsive encephalopathy associated with autoimmune thyroiditis
description	A few patients with Hashimoto’s thyroiditis or Graves’ disease develop a multiform syndrome of the central nervous system (CNS) termed Hashimoto’s encephalopathy or steroid-responsive encephalopathy associated with autoimmune thyroid disease (HE/SREAT). They have high levels of thyroid autoantibodies (TgAb, TPOAb and/or TSH-R-Ab) in blood and cerebrospinal fluid. Autoantibodies against alpha-enolase, aldehyde reductase-I (AKRIA) and/or dimethylargininase-I (DDAHI), proteins expressed in the CNS among other tissues, were detected in the blood and, when searched, in the cerebrospinal fluid of HE/SREAT patients. Recently, we reported that alpha-enolase, AKRIA and DDAHI share local sequence homology with each of the three autoantigens (TgAb, TPOAb, TSH-R-Ab), often in epitope-containing segments of the thyroid autoantigens. We hypothesized that there might be additional CNS-expressed proteins homologous to thyroid autoantigens, possibly overlapping known epitopes of the thyroid autoantigens. We used bioinformatic methods to address this hypothesis.Six, 27 and 47 of 46,809 CNS-expressed proteins share homology with TSH-R, Tg and TPO, respectively. The homologous regions often contain epitopes, and some match regions of thyroid autoantigens which have homology with alpha-enolase, AKRIA and/or DDAHI. Several of the aforementioned proteins are present in CNS areas that show abnormalities at neuroimaging in HE/SREAT patients. Furthermore, autoantibodies against some of the said six, 27 and 47 proteins were reported to be associated with a number of autoimmune diseases.Not only we validated our hypothesis, but we think that such a variety of potential CNS targets for thyroid Ab against epitopes contained in regions that have local homology with CNS proteins may explain the polymorphic phenotypes of HE/SREAT. Only when elevated amounts of these Ab are synthesized and trespass the blood-brain barrier, HE/SREAT appears. This might explain why HE/SREAT is so relatively rare.
format	article
author	Salvatore Benvenga Alessandro Antonelli Poupak Fallahi Carmen Bonanno Carmelo Rodolico Fabrizio Guarneri
author_facet	Salvatore Benvenga Alessandro Antonelli Poupak Fallahi Carmen Bonanno Carmelo Rodolico Fabrizio Guarneri
author_sort	Salvatore Benvenga
title	Amino acid sequence homology between thyroid autoantigens and central nervous system proteins: Implications for the steroid-responsive encephalopathy associated with autoimmune thyroiditis
title_short	Amino acid sequence homology between thyroid autoantigens and central nervous system proteins: Implications for the steroid-responsive encephalopathy associated with autoimmune thyroiditis
title_full	Amino acid sequence homology between thyroid autoantigens and central nervous system proteins: Implications for the steroid-responsive encephalopathy associated with autoimmune thyroiditis
title_fullStr	Amino acid sequence homology between thyroid autoantigens and central nervous system proteins: Implications for the steroid-responsive encephalopathy associated with autoimmune thyroiditis
title_full_unstemmed	Amino acid sequence homology between thyroid autoantigens and central nervous system proteins: Implications for the steroid-responsive encephalopathy associated with autoimmune thyroiditis
title_sort	amino acid sequence homology between thyroid autoantigens and central nervous system proteins: implications for the steroid-responsive encephalopathy associated with autoimmune thyroiditis
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/502aeba0361445e3a55e14e58d70cb5d
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Amino acid sequence homology between thyroid autoantigens and central nervous system proteins: Implications for the steroid-responsive encephalopathy associated with autoimmune thyroiditis

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