Obata Yoshinari, Fujita Yukari, Korechika Ayaka, Nakatani Rieko, Kozawa Junji, Shimomura Iichiro
Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
Department of Diabetes Care Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
JCEM Case Rep. 2025 May 15;3(7):luaf107. doi: 10.1210/jcemcr/luaf107. eCollection 2025 Jul.
A recent study revealed that the complex of thyrotropin receptors (TSHRs) and human leukocyte antigen (HLA) class II molecules within the thyroid gland, rather than TSHR alone, induces anti-TSHR autoantibody production by disrupting self-tolerance in Graves disease (GD). However, this complex has not yet been identified outside the thyroid gland. Complete removal of the thyroid gland typically reduces autoantibody titers by eliminating the antigen source. We present the case of a 51-year-old woman with GD and Graves ophthalmopathy who exhibited a marked increase in anti-TSHR autoantibodies concurrent with the development of pretibial myxedema (PTM) despite having undergone a total thyroidectomy. Immunohistological analysis of PTM tissues revealed the coexpression of TSHR and HLA class II molecules, forming a complex similar to that previously identified in the thyroid gland. These findings suggest that TSHR complexed with HLA class II molecules in PTM tissues may contribute to autoantibody production in this patient after total thyroidectomy, although the involvement of potential residual thyroid tissue cannot be entirely excluded. This case suggests that autoantibodies can be induced outside the thyroid gland and provides novel insights into the pathogenesis and progression of GD and related disorders.
最近的一项研究表明,在格雷夫斯病(GD)中,甲状腺内促甲状腺激素受体(TSHRs)与人类白细胞抗原(HLA)II类分子的复合物,而非单独的TSHR,通过破坏自身耐受性诱导抗TSHR自身抗体的产生。然而,这种复合物在甲状腺外尚未被发现。完全切除甲状腺通常会通过消除抗原来源降低自身抗体滴度。我们报告了一例51岁患有GD和格雷夫斯眼病的女性病例,尽管她已经接受了全甲状腺切除术,但在胫前黏液性水肿(PTM)出现时,抗TSHR自身抗体显著增加。对PTM组织的免疫组织学分析显示TSHR和HLA II类分子共表达,形成了一种与先前在甲状腺中发现的类似复合物。这些发现表明,PTM组织中与HLA II类分子复合的TSHR可能在全甲状腺切除术后导致该患者产生自身抗体,尽管不能完全排除潜在残留甲状腺组织的影响。该病例表明自身抗体可在甲状腺外诱导产生,并为GD及相关疾病的发病机制和进展提供了新的见解。