Objective biomarkers that can predict a severe disease course of autoimmune uveitis are lacking, and warranted for early identification of high-risk patients to improve visual outcome. The need for non-steroid immunomodulatory therapy (IMT) to control autoimmune uveitis is indicative of a more severe disease course. We used aptamer-based proteomics and a bioinformatic pipeline to uncover the serum protein network of 52 treatment-free patients and 26 healthy controls, and validation cohorts of 114 and 67 patients. Network-based analyses identified a highly co-expressed serum signature (n=85 proteins) whose concentration was consistently low in controls, but varied between cases. Patients that were positive for the signature at baseline showed a significantly increased risk for IMT during follow-up, independent of anatomical location of disease. In an independent cohort (n=114), we established robust risk categories that confirmed that patients with high levels of the signature at diagnosis had a significantly increased risk to start IMT during follow-up. Finally, we further validated the predictive power of the signature in a third cohort of 67 treatment-naive North-American patients. A serum protein signature was highly predictive for IMT in human autoimmune uveitis and may serve as an objective blood biomarker to aid in clinical-decision making.

中文翻译：

---

血清蛋白网络预测自身免疫性葡萄膜炎需要全身免疫调节治疗

缺乏可预测自身免疫性葡萄膜炎严重病程的客观生物标志物，有必要及早识别高危患者以改善视力结果。需要非类固醇免疫调节疗法 (IMT) 来控制自身免疫性葡萄膜炎，这表明病程更严重。我们使用基于适体的蛋白质组学和生物信息学管道来揭示 52 名未接受治疗的患者和 26 名健康对照者的血清蛋白网络，以及 114 名和 67 名患者的验证队列。基于网络的分析确定了一个高度共表达的血清特征（n = 85 个蛋白质），其浓度在对照中始终较低，但在不同情况下有所不同。基线时标记为阳性的患者在随访期间显示出 IMT 风险显着增加，与疾病的解剖位置无关。在一个独立队列 (n=114) 中，我们建立了稳健的风险类别，证实诊断时具有高水平特征的患者在随访期间开始 IMT 的风险显着增加。最后，我们进一步验证了第三组 67 名未接受过治疗的北美患者的特征的预测能力。血清蛋白特征对人自身免疫性葡萄膜炎中的 IMT 具有高度预测性，可作为客观的血液生物标志物以帮助临床决策。