Ifakara Health Institute, Bagamoyo, Tanzania.
Swiss Tropical and Public Health Institute, Basel, Switzerland.
PLoS One. 2018 Aug 29;13(8):e0202525. doi: 10.1371/journal.pone.0202525. eCollection 2018.
A quarter of the world's population is estimated to be infected with Myobacterium tuberculosis (Mtb). Infection is detected by immune response to M. tuberculosis antigens using either tuberculin skin test (TST) and interferon gamma release (IGRA's), tests which have low sensitivity in immunocompromised. IL-7 is an important cytokine for T-cell function with potential to augment cytokine release in in-vitro assays. This study aimed to determine whether the addition of IL-7 in interferon-gamma release assays (IGRAs) improves its diagnostic performance of Mtb infection.
44 cases with confirmed TB and 45 household contacts without TB were recruited and 1ml of blood was stimulated in two separate IGRA's tube set: one set of standard Quantiferon TB gold tubes mitogen, TB antigen and TB Nil; one set of customized Quantiferon TB gold tubes with added IL-7. Following IFN-γ and IP-10 release was determined using ELISA.
We found that the addition of IL-7 led to significantly higher release of IFN-γ in individuals with active TB from 4.2IU/ml (IQR 1.4-6.9IU/ml) to 5.1IU/ml (IQR 1.5-8.1IU/ml, p = 0.0057), and we found an indication of a lower release of both IFN-γ and IP-10 in participants with negative tests.
In TB cases addition of IL-7 in IGRA tubes augments IFN-γ but not IP-10 release, and seems to lower the response in controls. Whether IL-7 boosted IGRA holds potential over standard IGRA needs to be confirmed in larger studies in high and low TB incidence countries.
据估计,全球四分之一的人口感染了结核分枝杆菌(Myobacterium tuberculosis,Mtb)。通过免疫反应检测感染,使用结核菌素皮肤试验(TST)和干扰素γ释放(IGRA)检测,这些检测在免疫功能低下者中的敏感性较低。IL-7 是 T 细胞功能的重要细胞因子,具有增强细胞因子在体外检测中释放的潜力。本研究旨在确定在干扰素γ释放检测(IGRA)中添加 IL-7 是否能提高其对 Mtb 感染的诊断性能。
招募了 44 例确诊为结核病的病例和 45 例未患结核病的家庭接触者,并在两套独立的 IGRA 管中刺激 1ml 血液:一套是标准的 Quantiferon TB 金管刺激物、TB 抗原和 TB 无;另一套是添加了 IL-7 的定制的 Quantiferon TB 金管。采用 ELISA 法测定 IFN-γ和 IP-10 的释放情况。
我们发现,在活动性结核病患者中,添加 IL-7 导致 IFN-γ的释放显著增加,从 4.2IU/ml(IQR 1.4-6.9IU/ml)增加到 5.1IU/ml(IQR 1.5-8.1IU/ml,p=0.0057),我们发现阴性检测结果的个体 IFN-γ和 IP-10 的释放都有降低的趋势。
在结核病病例中,在 IGRA 管中添加 IL-7 可增强 IFN-γ但不增强 IP-10 的释放,并且似乎降低了对照者的反应。IL-7 增强的 IGRA 是否比标准 IGRA 具有潜力,需要在高和低结核病发病率国家的更大规模研究中加以证实。