Clinical Infection Medicine, Department of Translational Medicine, Lund University, Malmö, Sweden; Armauer Hansen Research Institute, Addis Ababa, Ethiopia.
Clinical Infection Medicine, Department of Translational Medicine, Lund University, Malmö, Sweden; Clinical Microbiology, Division of Laboratory Medicine, Lund, Sweden.
Tuberculosis (Edinb). 2020 Sep;124:101984. doi: 10.1016/j.tube.2020.101984. Epub 2020 Aug 12.
Borderline interferon-gamma (IFN-γ) results (near the cut-off level 0.35 IU/ml) occur in QuantiFERON (QFT) assays. We investigated the performance of alternative biomarkers for classification of latent tuberculosis infection (LTBI) status in pregnant women with borderline QFT IFN-γ responses. Pregnant women (n = 96) were identified from a cohort study in Ethiopia, based on QFT-Plus IFN-γ results (QFT-low: <0.20 IU/ml, n = 33; QFT-borderline: 0.20-0.70 IU/ml, n = 31; QFT-high: >0.70 IU/ml, n = 32), including 12 HIV-positive individuals in each group and with 20 HIV-negative non-pregnant women from the same cohort with QFT IFN-γ <0.20 IU/ml as controls. Concentrations of 8 markers (IL-1ra, IL-6, IL-8, IP-10, MCP-1, MCP-2, osteopontin and resistin) were measured in whole blood QFT supernatants, stimulated separately with TB1 and TB2 antigens. K-nearest neighbor analysis (KNN) was used to classify participants with regard to likelihood of LTBI. Concentrations of MCP-2, IP-10 and IL-1ra were higher in QFT-borderline compared to QFT-low participants in both antigen stimulations (p < 0.001). KNN classification indicated high likelihood of LTBI in 13/31 (42%) women with QFT-borderline IFN-γ results. MCP-2, IP-10 and IL-1ra expressed in whole blood after TB antigen stimulation may be considered as alternative biomarkers for classification of LTBI status in pregnant women with borderline QFT IFN-γ results.
边界干扰素-γ（IFN-γ）结果（接近 0.35 IU/ml 的截止水平）出现在 QuantiFERON（QFT）检测中。我们研究了替代生物标志物在具有边界 QFT IFN-γ 反应的孕妇中对潜伏性结核感染（LTBI）状态进行分类的性能。根据 QFT-Plus IFN-γ 结果（QFT-低：<0.20 IU/ml，n=33；QFT-边界：0.20-0.70 IU/ml，n=31；QFT-高：>0.70 IU/ml，n=32），从埃塞俄比亚的一项队列研究中确定了孕妇（n=96），包括每组中的 12 名 HIV 阳性个体和来自同一队列的 20 名 HIV 阴性非孕妇，他们的 QFT IFN-γ<0.20 IU/ml 作为对照。在 TB1 和 TB2 抗原分别刺激下，测量全血 QFT 上清液中 8 种标志物（IL-1ra、IL-6、IL-8、IP-10、MCP-1、MCP-2、骨桥蛋白和抵抗素）的浓度。使用 K-最近邻分析（KNN）根据 LTBI 的可能性对参与者进行分类。在两种抗原刺激下，QFT-边界参与者的 MCP-2、IP-10 和 IL-1ra 浓度均高于 QFT-低参与者（p<0.001）。KNN 分类表明，在 31 名（42%）具有边界 QFT IFN-γ 结果的女性中，LTBI 的可能性很高。在 TB 抗原刺激后全血中表达的 MCP-2、IP-10 和 IL-1ra 可被视为具有边界 QFT IFN-γ 结果的孕妇 LTBI 状态分类的替代生物标志物。
