Translational Research Unit National Institute for Infectious Diseases, Lazzaro Spallanzani IRCCS, Rome, Italy.
Regional TB Reference Centre, Istituto Villa Marelli, Ospedale Niguarda, Milano, Italy.
Sci Rep. 2018 Oct 23;8(1):15626. doi: 10.1038/s41598-018-33825-w.
Lack of biomarkers for treatment monitoring is listed among the main requirements for next generation assays, as identified globally among tuberculosis (TB) researchers. In this study, we evaluated in a low TB endemic country such as Italy, the effect of preventive therapy on the results obtained in the QuantiFERON TB Plus (QFT-Plus), in a cohort of subjects with latent TB infection (LTBI) and active TB. We found that TB therapy significantly decreased IFN-γ values and number of responders to TB1- and TB2- peptides stimulation in both LTBI and active TB patients. Stratifying LTBI subjects according to the type of preventive TB therapy used, we found that INH treatment but not INH and RIF significantly decreased IFN-γ production. Stratifying the active TB patients according the microbiological status, we found that TB therapy significantly decreased IFN-γ response to antigen present in QFT-Plus test in patients with clinical diagnosis compared to those with a microbiological diagnosis. In conclusions, we demonstrated that TB therapy decreases IFN-γ level in response to antigen present in QFT-Plus test in LTBI and active TB patients. Future studies are needed to better characterize Mtb-specifc response as a potential marker for monitoring TB therapy and preventive treatment effects.
缺乏治疗监测的生物标志物被列为下一代检测的主要要求之一,这是全球结核病(TB)研究人员共同确定的。在这项研究中,我们在意大利等结核病低流行国家评估了预防性治疗对潜伏性结核感染(LTBI)和活动性 TB 患者中 QuantiFERON TB Plus(QFT-Plus)检测结果的影响。我们发现,TB 治疗显著降低了 LTBI 和活动性 TB 患者对 TB1 和 TB2 肽刺激的 IFN-γ 值和应答者数量。根据使用的预防性 TB 治疗类型对 LTBI 受试者进行分层,我们发现 INH 治疗而非 INH 和 RIF 治疗显著降低了 IFN-γ 的产生。根据微生物学状态对活动性 TB 患者进行分层,我们发现与微生物学诊断相比,临床诊断的患者 TB 治疗显著降低了 QFT-Plus 检测中存在的抗原的 IFN-γ 反应。总之,我们证明了 TB 治疗降低了 LTBI 和活动性 TB 患者对 QFT-Plus 检测中存在的抗原的 IFN-γ 水平。需要进一步的研究来更好地描述 Mtb 特异性反应作为监测 TB 治疗和预防性治疗效果的潜在标志物。