Objective

Thyroid eye disease (TED) is an immune-mediated disorder of the eye. Intravenous glucocorticoid (GC) is the first-line treatment for patients with active moderate-to-severe TED. However, the response rate is between 50% and 80%. There are still no simple and reliable markers of responsiveness to GC therapy. We aimed to explore the possible role of miR-146a and miR-21 as predictors of responsiveness to GC treatment in TED.

Methods

We carried out a prospective longitudinal study on 30 consecutive adult patients with active moderate-to-severe TED and eligible for GC therapy. All patients received the standard GC treatment with methylprednisolone i.v. In cases of progressive worsening of Gorman Score for diplopia or with duction restriction <30° in at least two consecutive controls, patients also underwent orbital radiotherapy. Response to GC treatment was defined as a decrease of two or more points in the clinical activity score (CAS) or CAS <4/10 at 24 weeks. Circulating miRNAs were extracted from patients’ serum and quantified by real-time PCR.

Results

Twenty-three (77%) patients responded to GC. Thyroid surgery, higher CAS, greater proptosis and higher pre-treatment circulating levels of miR-146a emerged as predictive factors of responsiveness to GC. A ROC analysis revealed that miR-146a could predict responsiveness to GC with a positive predictive value of 100%.

Conclusion

This is the first study investigating the role of pre-treatment circulating miR-21 and miR-146a to predict responsiveness to GC in TED. miR-146a emerged as a simple, objective, new marker of GC sensitivity that could be used to avoid ineffective administration of GC therapy to TED patients.

中文翻译：

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循环miR-​​146a预测甲状腺眼病中的糖皮质激素反应

客观的

甲状腺眼病（TED）是一种免疫介导的眼部疾病。静脉注射糖皮质激素 (GC) 是活动性中度至重度 TED 患者的一线治疗方法。然而，回复率在 50% 到 80% 之间。仍然没有简单可靠的 GC 治疗反应标记。我们的目的是探讨 miR-146a 和 miR-21 作为 TED 中 GC 治疗反应预测因子的可能作用。

方法

我们对 30 名连续患有活动性中度至重度 TED 且符合 GC 治疗资格的成年患者进行了一项前瞻性纵向研究。所有患者均接受静脉注射甲基泼尼松龙的标准 GC 治疗。如果复视 Gorman 评分进行性恶化或至少两个连续对照的诱导受限 <30°，则患者还接受了眼眶放射治疗。对 GC 治疗的反应定义为 24 周时临床活动评分 (CAS) 降低 2 分或以上或 CAS <4/10。从患者血清中提取循环 miRNA，并通过实时 PCR 进行定量。

结果

二十三名 (77%) 患者对 GC 有反应。甲状腺手术、较高的 CAS、较大的突眼和较高的治疗前 miR-146a 循环水平成为 GC 反应性的预测因素。ROC 分析显示，miR-146a 可以预测 GC 的反应性，阳性预测值为 100%。

结论

这是第一项研究治疗前循环 miR-21 和 miR-146a 在预测 TED GC 反应中的作用。miR-146a 成为一种简单、客观、新的 GC 敏感性标记物，可用于避免对 TED 患者进行无效的 GC 治疗。