Department of Endocrinology, Shanghai Fifth People's Hospital, Fudan University, Shanghai 200240, China.
Sci Adv. 2024 Aug 2;10(31):eadi8646. doi: 10.1126/sciadv.adi8646. Epub 2024 Jul 31.
Previous observational studies found associations between infection and autoimmune thyroid diseases (AITDs), but the causal nature of this association is still uncertain. We investigated the causal effect of six crucial antibodies against on AITDs using a bidirectional Mendelian randomization (MR). We found that anti- outer membrane protein (OMP) significantly increased the risk of hyperthyroidism and Graves' disease (GD). In addition, our reverse MR analysis indicated that hyperthyroidism could increase the levels of cytotoxin-associated gene A and OMP antibodies. We also observed causal roles of GD on anti- OMP. Our analyses indicate the mutual effects of infection and AITDs, suggesting the existence of a gut-thyroid axis. These results also provide evidence of the bidirectional causal association between anti- OMP with hyperthyroidism and GD, resulting in a vicious circle.
先前的观察性研究发现感染与自身免疫性甲状腺疾病(AITD)之间存在关联,但这种关联的因果性质仍不确定。我们使用双向 Mendelian 随机化(MR)研究了六种针对 的关键抗体与 AITD 之间的因果关系。我们发现抗外膜蛋白(OMP)抗体显著增加了甲状腺功能亢进症和格雷夫斯病(GD)的风险。此外,我们的反向 MR 分析表明,甲状腺功能亢进症会增加细胞毒素相关基因 A 和 OMP 抗体的水平。我们还观察到 GD 对抗 OMP 的因果作用。我们的分析表明感染和 AITD 之间存在相互作用,提示存在肠道-甲状腺轴。这些结果还为抗 OMP 与甲状腺功能亢进症和 GD 之间存在双向因果关联提供了证据,导致恶性循环。