{"title":"甲状腺自身抗原和中枢神经系统蛋白之间的氨基酸序列同源性:与自身免疫性甲状腺炎相关的类固醇反应性脑病的意义","authors":"Salvatore Benvenga , Alessandro Antonelli , Poupak Fallahi , Carmen Bonanno , Carmelo Rodolico , Fabrizio Guarneri","doi":"10.1016/j.jcte.2021.100274","DOIUrl":null,"url":null,"abstract":"<div><p>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.</p><p>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.</p><p>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.</p></div>","PeriodicalId":46328,"journal":{"name":"Journal of Clinical and Translational Endocrinology","volume":null,"pages":null},"PeriodicalIF":4.2000,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8609095/pdf/","citationCount":"2","resultStr":"{\"title\":\"Amino acid sequence homology between thyroid autoantigens and central nervous system proteins: Implications for the steroid-responsive encephalopathy associated with autoimmune thyroiditis\",\"authors\":\"Salvatore Benvenga , Alessandro Antonelli , Poupak Fallahi , Carmen Bonanno , Carmelo Rodolico , Fabrizio Guarneri\",\"doi\":\"10.1016/j.jcte.2021.100274\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>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.</p><p>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.</p><p>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.</p></div>\",\"PeriodicalId\":46328,\"journal\":{\"name\":\"Journal of Clinical and Translational Endocrinology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.2000,\"publicationDate\":\"2021-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8609095/pdf/\",\"citationCount\":\"2\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Clinical and Translational Endocrinology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2214623721000260\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Clinical and Translational Endocrinology","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2214623721000260","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 2
摘要
少数桥本甲状腺炎或格雷夫斯病患者发展为多形式中枢神经系统综合征(CNS),称为桥本脑病或类固醇反应性脑病伴自身免疫性甲状腺疾病(HE/SREAT)。他们在血液和脑脊液中有高水平的甲状腺自身抗体(TgAb、TPOAb和/或TSH-R-Ab)。针对α -烯醇化酶、醛还原酶- i (AKRIA)和/或二甲基精氨酸酶- i (DDAHI)的自身抗体在HE/ sgreat患者的血液和脑脊液中检测到,这些蛋白在中枢神经系统和其他组织中表达。最近,我们报道了α -烯醇酶,AKRIA和DDAHI与三种自身抗原(TgAb, TPOAb, TSH-R-Ab)具有局部序列同源性,通常位于甲状腺自身抗原的表位片段中。我们推测可能存在其他cns表达的与甲状腺自身抗原同源的蛋白,可能与已知的甲状腺自身抗原表位重叠。我们使用生物信息学方法来解决这一假设。在46,809个cns表达蛋白中,分别有6个、27个和47个与TSH-R、Tg和TPO具有同源性。同源区域通常包含表位,一些甲状腺自身抗原的匹配区域与α -烯醇酶、AKRIA和/或DDAHI具有同源性。上述几种蛋白存在于HE/ great患者神经影像学表现异常的中枢神经系统区域。此外,据报道,针对上述6、27和47蛋白中的一些的自身抗体与许多自身免疫性疾病有关。我们不仅验证了我们的假设,而且我们认为甲状腺Ab针对与CNS蛋白具有局部同源性的区域所含的表位的潜在CNS靶点的多样性可能解释了HE/SREAT的多态性表型。只有当这些Ab的合成量升高并越过血脑屏障时,HE/ great才会出现。这也许可以解释为什么HE/ great是如此的罕见。
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 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.