Department of Endocrinology and Metabolism, Institute of Endocrinology, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, Shenyang 110001, PR China.
Clin Exp Immunol. 2022 Dec 15;210(2):187-198. doi: 10.1093/cei/uxac086.
Anti-alpha-enolase autoantibodies have not only been found to play an important role in autoimmune diseases but also cause neurological damage in adults. In this study, a pregnant mouse model with high serum alpha-enolase (ENO1)-specific antibody (ENO1Ab) was established by immunization with ENO1 protein to explore the effects of maternal circulatory ENO1Ab on the brain development in offspring. The pups showed impaired learning and memory abilities with obviously thinner tight junctions in the brain tissue. IgG deposits colocalized with both ENO1 protein and complement 3 (C3), and the membrane attack complex was obviously detectable in the brain tissues of pups from dams with high serum ENO1Ab expression. Our findings suggest that highly expressed ENO1Ab in the maternal circulation can pass through the blood-placenta-barrier and the compromised blood-brain barrier into the brain tissues of offspring and may cause neurological development impairment mainly through complement-dependent cytotoxicity.
抗α-烯醇化酶自身抗体不仅在自身免疫性疾病中发挥重要作用，而且还会导致成年人的神经损伤。在这项研究中，通过用 ENO1 蛋白免疫妊娠小鼠建立了血清α-烯醇化酶（ENO1）特异性抗体（ENO1Ab）水平较高的小鼠模型，以探讨母体循环 ENO1Ab 对后代大脑发育的影响。结果发现，与对照组相比，仔鼠的学习和记忆能力受损，脑组织中的紧密连接明显变薄。IgG 沉积物与 ENO1 蛋白和补体 3（C3）共定位，在母鼠血清中 ENO1Ab 表达水平较高的仔鼠脑组织中明显可检测到膜攻击复合物。这些发现表明，母体循环中高表达的 ENO1Ab 可以穿过血-胎盘屏障和受损的血脑屏障进入后代的脑组织，并可能主要通过补体依赖性细胞毒性导致神经发育损伤。
