Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia.
Molecular Thyroid Research Laboratory, Department of Medicine I, Johannes Gutenberg University [JGU] Medical Center, Mainz, Germany.
J Endocrinol Invest. 2023 Nov;46(11):2309-2317. doi: 10.1007/s40618-023-02085-5. Epub 2023 Apr 5.
Graves' orbitopathy (GO) is a specific inflammatory disorder of the orbit characterized by a highly heterogeneous clinical phenotype. The role of thyrotropin receptor antibodies (TSH-R-Ab) has been widely researched, however there is still no evidence that these antibodies have a direct pathogenic role in this pathology. The aim of this study was to examine their relation to the individual clinical features of GO.
Ninety-one consecutive patients with GO were recruited. Total antibody concentration (TSH-R binding inhibitory immunoglobulins, TBII) and their functional activity (stimulating TSH-R-Ab, TSAb) were measured using binding immunoassay and cell-based bioassay, respectively.
Both TSAb and TBII levels were significantly associated to the clinical parameters of GO activity. TSAb was a more sensitive serological marker compared to TBII pertaining to eyelid retraction and edema, proptosis, extra-orbital muscle disorders, diplopia, irritable eye symptoms, and photophobia. TSAb, but not TBII, was a significant predictive marker of conjunctival redness, chemosis, caruncle/plica inflammation, eye irritation, and orbital pain, (odds ratio: 3.096, p = 0.016; 5.833, p = 0.009; 6.443, p = 0.020; 3.167, p = 0.045; 2.893, p = 0.032; versus 2.187, p = 0.093; 2.775, p = 0.081; 3.824, p = 0.055; 0.952, p = 0.930; 2.226, p = 0.099, respectively). Neither TSAb nor TBII correlated with the level of proptosis (ρ = 0.259, p = 0.090, and ρ = 0.254, p = 0.104, respectively), however rising TSAb levels were strongly associated to the level of proptosis.
TSH-R-Ab were significantly associated with GO's phenotype. Especially TSAb, as a sensitive and predictive serological biomarker, can improve diagnosis and management of GO.
格雷夫斯眼病（GO）是一种特定的眼眶炎症性疾病，其特征为临床表现高度异质性。促甲状腺激素受体抗体（TSH-R-Ab）的作用已被广泛研究，但仍没有证据表明这些抗体在该病理中具有直接的致病作用。本研究旨在探讨其与 GO 个体临床特征的关系。
招募了 91 例连续的 GO 患者。使用结合免疫测定法和基于细胞的生物测定法分别测量总抗体浓度（TSH-R 结合抑制免疫球蛋白，TBII）和其功能活性（刺激 TSH-R-Ab，TSAb）。
TSAb 和 TBII 水平均与 GO 活动的临床参数显著相关。与眼睑退缩和水肿、眼球突出、眼外肌疾病、复视、眼部刺激症状和畏光相比，TSAb 是一种更敏感的血清学标志物。TSAb 是结膜充血、水肿、泪阜/睑板炎、眼部刺激、眶痛的显著预测标志物（优势比：3.096，p=0.016；5.833，p=0.009；6.443，p=0.020；3.167，p=0.045；2.893，p=0.032；与 2.187，p=0.093；2.775，p=0.081；3.824，p=0.055；0.952，p=0.930；2.226，p=0.099），而 TBII 则没有。TSAb 和 TBII 均与眼球突出程度无相关性（ρ=0.259，p=0.090，和 ρ=0.254，p=0.104），但是 TSAb 水平升高与眼球突出程度强烈相关。
TSH-R-Ab 与 GO 的表型显著相关。特别是作为一种敏感和预测性的血清生物标志物的 TSAb，可以改善 GO 的诊断和管理。
