Department of Ophthalmology, University of Indonesia & Cipto Mangunkusumo Hospital Kirana, Jakarta, Indonesia.
Laboratory of Medical Immunology, Erasmus Medical Center, Rotterdam, the Netherlands.
PLoS One. 2018 Oct 18;13(10):e0206073. doi: 10.1371/journal.pone.0206073. eCollection 2018.
QuantiFERON-Gold TB (QFT)-positive patients with undetermined cause of uveitis are problematic in terms of whether to diagnose and treat them for tuberculosis (TB). Here, we investigated whether peripheral blood expression of type 1 interferon (IFN)-inducible genes may be of use to stratify QFT-positive patients with uveitis into groups of high versus low risk of having active TB-associated uveitis. We recruited all new uveitis patients in Cipto Mangunkusumo Hospital, Jakarta, Indonesia for one year. We included 12 patients with uveitis and clinically diagnosed active pulmonary TB, 58 QFT-positive patients with uveitis of unknown cause, 10 newly diagnosed sputum-positive active pulmonary TB patients without uveitis and 23 QFT-negative healthy controls. Expression of 35 type 1 IFN-inducible genes was measured in peripheral blood cells from active pulmonary TB patients without uveitis and healthy controls. Differentially expressed genes were identified and used for further clustering analyses of the uveitis groups. A type-1 IFN gene signature score was calculated and the optimal cut-off value for this score to differentiate active pulmonary TB from healthy controls was determined and applied to QFT-positive patients with uveitis of unknown cause. Ten type 1 IFN-inducible genes were differentially expressed between active pulmonary TB and healthy controls. Expression of these 10 genes in QFT-positive patients with uveitis of unknown cause revealed three groups: 1); patients resembling active pulmonary TB, 2); patients resembling healthy controls, and 3); patients displaying an in-between gene expression pattern. A type 1 IFN gene signature score ≥5.61 displayed high sensitivity (100%) and specificity (91%) for identification of active TB. Application of this score to QFT-positive patients with uveitis of unknown cause yielded two groups with expected different likelihood (high vs. low) of having active-TB uveitis, and therefore may be useful in clinical management decisions.
因葡萄膜炎病因不明而 QFT-阳性的患者是否需要诊断和治疗结核病（TB）存在问题。在此，我们研究了外周血 1 型干扰素（IFN）诱导基因的表达是否可用于将 QFT-阳性的葡萄膜炎患者分为活动性 TB 相关葡萄膜炎高风险和低风险组。我们在印度尼西亚雅加达 Cipto Mangunkusumo 医院招募了所有新的葡萄膜炎患者，为期一年。我们纳入了 12 例有葡萄膜炎和临床诊断活动性肺结核的患者，58 例有葡萄膜炎但病因不明的 QFT-阳性患者，10 例新诊断的痰阳性活动性肺结核且无葡萄膜炎的患者和 23 例 QFT-阴性的健康对照者。我们测量了无葡萄膜炎的活动性肺结核患者和健康对照者外周血细胞中 35 种 1 型 IFN 诱导基因的表达。确定差异表达基因，并对葡萄膜炎组进行进一步聚类分析。计算 1 型 IFN 基因特征评分，并确定该评分区分活动性肺结核和健康对照的最佳截断值，并应用于病因不明的 QFT-阳性葡萄膜炎患者。10 种 1 型 IFN 诱导基因在活动性肺结核和健康对照者之间表达差异。在病因不明的 QFT-阳性葡萄膜炎患者中这 10 种基因的表达显示出 3 个组：1）；类似于活动性肺结核的患者，2）；类似于健康对照者的患者，和 3）；表达处于两者之间的患者。1 型 IFN 基因特征评分≥5.61 对识别活动性 TB 具有高灵敏度（100%）和特异性（91%）。将该评分应用于病因不明的 QFT-阳性葡萄膜炎患者，得到两组，其发生活动性-TB 葡萄膜炎的可能性（高与低）不同，因此可能对临床管理决策有用。
