Autoimmune thyroiditis (AIT)-related brain damage is one of most severe extrathyroidal manifestations of AIT, but the mechanism remains unclear. In this study, we confirmed that protein disulfide-isomerase A3 (PDIA3) is expressed in both thyroid and brain tissues of mouse, and found the significantly increased serum levels of anti-PDIA3 antibody (PDIA3Ab) in classical mouse models of thyroiditis. In addition, we investigated the PDIA3-specific autoimmune reaction in thyroid and brain tissues in a mouse model with high-serum PDIA3Ab induced by immunization with recombinant PDIA3 protein. PDIA3-immunized mice had elevated serum thyrotropin and impaired learning and memory. PDIA3-expressing cells had IgG deposition, and IgG colocalized with C3 in the thyroid and brain tissues of PDIA3-immunized mice, resulting in membrane attack complex formation. Our results suggest that PDIA3 protein may be a common autoantigen shared by the thyroid and brain tissues and involve in the thyroidal and intracerebral damage through activating complement system.

中文翻译：

---

蛋白二硫键异构酶A3作为自身抗原在成年小鼠自身免疫性甲状腺炎和相关脑损伤的发病机理中的作用。

自身免疫性甲状腺炎（AIT）相关的脑损伤是AIT最严重的甲状腺外表现之一，但其机制仍不清楚。在这项研究中，我们证实了蛋白质二硫键异构酶A3（PDIA3）在小鼠的甲状腺和脑组织中均有表达，并且在经典的甲状腺炎小鼠模型中发现抗PDIA3抗体（PDIA3Ab）的血清水平显着升高。此外，我们在小鼠模型中用重组PDIA3蛋白免疫诱导的高血清PDIA3Ab，研究了甲状腺和脑组织中PDIA3特异性自身免疫反应。PDIA3免疫的小鼠血清促甲状腺激素水平升高，学习和记忆受损。表达PDIA3的细胞具有IgG沉积，并且IgG与C3在经PDIA3免疫的小鼠的甲状腺和脑组织中共定位，导致形成膜攻击复合物。