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Experimental evidence for alpha enolase as one potential autoantigen in the pathogenesis of both autoimmune thyroiditis and its related encephalopathy.
International Immunopharmacology ( IF 4.8 ) Pub Date : 2020-05-19 , DOI: 10.1016/j.intimp.2020.106563
Yihan Lu 1 , Juan Qin 1 , Yang Xiang 1 , Rongli Sun 1 , Yan Feng 1 , Hongmei Zhang 1 , Shuangning Ding 1 , Jing Li 1 , Zhongyan Shan 1 , Weiping Teng 1
Affiliation  

Alpha-enolase (ENO1) is a ubiquitous protein. Patients with autoimmune thyroiditis-associated encephalopathy have high serum ENO1Ab titers. We aimed to explore whether ENO1Ab was the pathogenic antibody in the thyroid and brain. The serum ENO1Ab titers were significantly increased in the mice immunized with Thyroglobulin (Tg). And in the mice immunized with ENO1, serum levels of both TgAb and thyroid-stimulating hormone (TSH) were significantly increased. Obvious CD16+ cell infiltration, IgG deposit and cleaved caspase-3 were observed in the thyroid of ENO1-immunized mice. Spatial learning and memory abilities and synaptic functions were impaired in ENO1-immunized mice. Furthermore, the expression levels of Iba-1, GFAP, interlukin-6, CDK5, and phosphorylated tau were increased, and endothelial tight junction proteins were decreased in the brain of ENO1-immunized mice. These results suggest that ENO1Ab can cause thyrocyte damage via ADCC effect and impair cerebral function by disrupting the blood–brain barrier.



中文翻译:

在自身免疫性甲状腺炎及其相关脑病的发病机理中,α烯醇化酶是一种潜在的自身抗原的实验证据。

α-烯醇化酶(ENO1)是一种普遍存在的蛋白质。自身免疫性甲状腺炎相关性脑病患者的血清ENO1Ab滴度较高。我们旨在探讨ENO1Ab是否是甲状腺和大脑中的致病性抗体。甲状腺球蛋白(Tg)免疫的小鼠的血清ENO1Ab滴度显着增加。在用ENO1免疫的小鼠中,血清TgAb和促甲状腺激素(TSH)均显着增加。明显的CD16 +在经ENO1免疫的小鼠的甲状腺中观察到细胞浸润,IgG沉积和caspase-3裂解。ENO1免疫的小鼠的空间学习和记忆能力和突触功能受损。此外,在经ENO1免疫的小鼠的大脑中,Iba-1,GFAP,白介素6,CDK5和磷酸化tau的表达水平增加,而内皮紧密连接蛋白减少。这些结果表明,ENO1Ab可以通过ADCC效应引起甲状腺细胞损伤,并通过破坏血脑屏障来损害脑​​功能。

更新日期:2020-05-19
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