Multi-country evaluation of RISK6, a 6-gene blood transcriptomic signature, for tuberculosis diagnosis and treatment monitoring.
Multi-country evaluation of RISK6, a 6-gene blood transcriptomic signature, for tuberculosis diagnosis and treatment monitoring.
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DOI：
10.1038/s41598-021-93059-1
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发表时间：
2021-07-01
影响因子：
4.6
通讯作者：
HINTT working group within the GABRIEL network
中科院分区：
文献类型：
--
作者：
Bayaa R;Ndiaye MDB;Chedid C;Kokhreidze E;Tukvadze N;Banu S;Uddin MKM;Biswas S;Nasrin R;Ranaivomanana P;Raherinandrasana AH;Rakotonirina J;Rasolofo V;Delogu G;De Maio F;Goletti D;Endtz H;Ader F;Hamze M;Ismail MB;Pouzol S;Rakotosamimanana N;Hoffmann J;HINTT working group within the GABRIEL network
迫切需要非痰结核病检测。在这里，我们评估了 RISK6（一种人类血液转录组特征）在结核病筛查、分诊和治疗监测方面的性能。 RISK6 的性能还与两种 IGRA 的性能进行了比较：一种基于 RD1 抗原（QuantiFERON-TB Gold Plus、QFT-P、Qiagen），另一种基于耻垢分枝杆菌中表达的重组结核分枝杆菌 HBHA（IGRA-rmsHBHA）。在孟加拉国、格鲁吉亚、黎巴嫩和马达加斯加进行的这项多中心前瞻性巢式病例对照研究中，招募了经细菌学证实的活动性肺结核（ATB）、潜伏性结核感染（LTBI）的成年非免疫功能低下患者和健康捐献者（HD）。 ATB 患者在治疗期间和治疗后进行随访。使用定量实时 PCR 评估血液 RISK6 评分，并通过受试者工作特征曲线下面积 (ROC AUC) 进行评估。 RISK6 区分 ATB 和 HD 的 AUC 为 0.94（95% CI 0.89-0.99），敏感性为 90.9%，特异性为 87.8%，从而实现了非痰结核筛查测试的最低 WHO 目标产品特征。此外，RISK6 的 AUC 为 0.93 (95% CI 0.85–1)，区分 ATB 和 LTBI 的敏感性为 90.9%，特异性为 88.5%。此外，RISK6 在区分结核感染阶段方面表现出比 IGRA-rmsHBHA（AUC 0.75，95% CI 0.69-0.82）更高的性能（AUC 0.90，95% CI 0.85-0.94）。最后，在 TB 治疗 2 个月后，RISK6 特征分数显着下降，并继续逐渐下降，直到治疗结束达到 HD 中获得的分数。我们确认了 RISK6 签名作为结核病分诊测试的性能及其在治疗监测方面的实用性。
There is a crucial need for non-sputum-based TB tests. Here, we evaluate the performance of RISK6, a human-blood transcriptomic signature, for TB screening, triage and treatment monitoring. RISK6 performance was also compared to that of two IGRAs: one based on RD1 antigens (QuantiFERON-TB Gold Plus, QFT-P, Qiagen) and one on recombinant M. tuberculosis HBHA expressed in Mycobacterium smegmatis (IGRA-rmsHBHA). In this multicenter prospective nested case–control study conducted in Bangladesh, Georgia, Lebanon and Madagascar, adult non-immunocompromised patients with bacteriologically confirmed active pulmonary TB (ATB), latent TB infection (LTBI) and healthy donors (HD) were enrolled. ATB patients were followed-up during and after treatment. Blood RISK6 scores were assessed using quantitative real-time PCR and evaluated by area under the receiver-operating characteristic curve (ROC AUC). RISK6 performance to discriminate ATB from HD reached an AUC of 0.94 (95% CI 0.89–0.99), with 90.9% sensitivity and 87.8% specificity, thus achieving the minimal WHO target product profile for a non-sputum-based TB screening test. Besides, RISK6 yielded an AUC of 0.93 (95% CI 0.85–1) with 90.9% sensitivity and 88.5% specificity for discriminating ATB from LTBI. Moreover, RISK6 showed higher performance (AUC 0.90, 95% CI 0.85–0.94) than IGRA-rmsHBHA (AUC 0.75, 95% CI 0.69–0.82) to differentiate TB infection stages. Finally, RISK6 signature scores significantly decreased after 2 months of TB treatment and continued to decrease gradually until the end of treatment reaching scores obtained in HD. We confirmed the performance of RISK6 signature as a triage TB test and its utility for treatment monitoring.
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作者：
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影响因子：
3.7
作者：
Chiacchio T;Delogu G;Vanini V;Cuzzi G;De Maio F;Pinnetti C;Sampaolesi A;Antinori A;Goletti D
通讯作者：
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影响因子：
4.6
作者：
Penn-Nicholson, Adam;Mbandi, Stanley Kimbung;Scriba, Thomas J.
通讯作者：
Scriba, Thomas J.