Shete Priya B, Ravindran Resmi, Chang Emily, Worodria William, Chaisson Lelia H, Andama Alfred, Davis J Lucian, Luciw Paul A, Huang Laurence, Khan Imran H, Cattamanchi Adithya
Division of Pulmonary and Critical Care Medicine, University of California- San Francisco and Zuckerberg San Francisco General Hospital, San Francisco CA United States of America.
Curry International Tuberculosis Center, University of California-San Francisco, San Francisco CA United States of America.
PLoS One. 2017 Aug 2;12(8):e0180122. doi: 10.1371/journal.pone.0180122. eCollection 2017.
Improved systematic screening of high-risk groups is a key component of the tuberculosis (TB) elimination strategy endorsed by the World Health Organization (WHO). We used a multiplex microbead immunoassay to measure antibody responses to 28 M. tuberculosis (M.tb) antigens, and assessed whether combinations of antibody responses achieve accuracy thresholds required for a TB screening test.
A random selection of plasma samples obtained from consecutive HIV-negative adults who were admitted to Mulago Hospital in Kampala, Uganda with cough ≥2 weeks' but <6 months' duration were analyzed for serological response to 28 M.tb antigens using an in-house multiplex microbead immunoassay. We compared the median difference of the antibody response to each antigen between patients with and without culture-confirmed TB, ranked each antigen according to variable importance (VIM), and assessed the sensitivity and specificity of combinations of antibody responses using an advanced classification algorithm, SuperLearner.
Among the 237 patients included in the analysis, 119 (50%) were female, median age was 32 years (IQR 25, 46), and 113 (48%) had TB. Median antibody levels to eight antigens were significantly different between patients with and without TB. A panel including eight of the top ranked antigens had a sensitivity of 90.6% (95% CI 89.4, 93.8) and a specificity of 88.6% (95% CI 78.2, 97.6) (Ag85B, Ag85A, Ag85C, Rv0934-P38, Rv3881, BfrB, Rv3873, and Rv2878c). With sensitivity constrained to be >90%, specificity remained close to 70% with as few as 3 antigens included in the panels.
Measuring antibody responses to combinations of antigens could facilitate TB screening and should be further evaluated in populations being targeted for systematic screening.
加强对高危人群的系统筛查是世界卫生组织（WHO）认可的结核病（TB）消除战略的关键组成部分。我们使用多重微珠免疫测定法来测量对28种结核分枝杆菌（M.tb）抗原的抗体反应，并评估抗体反应组合是否达到结核病筛查试验所需的准确性阈值。
从乌干达坎帕拉穆拉戈医院连续收治的咳嗽持续时间≥2周但<6个月的HIV阴性成年人中随机选取血浆样本，使用内部多重微珠免疫测定法分析其对28种M.tb抗原的血清学反应。我们比较了有和没有培养确诊结核病的患者对每种抗原的抗体反应的中位数差异，根据变量重要性（VIM）对每种抗原进行排名，并使用先进的分类算法SuperLearner评估抗体反应组合的敏感性和特异性。
在纳入分析的237例患者中，119例（50%）为女性，中位年龄为32岁（四分位间距25，46），113例（48%）患有结核病。有和没有结核病的患者对8种抗原的抗体水平中位数有显著差异。一个包含8种排名靠前抗原的组合的敏感性为90.6%（95%CI 89.4，93.8），特异性为88.6%（95%CI 78.2，97.6）（Ag85B、Ag85A、Ag85C、Rv0934-P38、Rv3881、BfrB、Rv3873和Rv2878c）。当敏感性限制在>90%时，组合中仅包含3种抗原时特异性仍接近70%。
测量对抗原组合的抗体反应可能有助于结核病筛查，应在目标进行系统筛查的人群中进一步评估。
