Table_2_The Use of TB-Specific Antigen/Phytohemagglutinin Ratio for Diagnosis and Treatment Monitoring of Extrapulmonary Tuberculosis.xls

Extrapulmonary tuberculosis (EPTB) has become more common in recent years; however, the diagnosis of EPTB remains a challenge. In this study, we analyzed the performance of the ratio of TB-specific antigen (TBAg) to phytohemagglutinin (PHA) (TBAg/PHA ratio) in T-SPOT.TB (T-SPOT) assay for diagnosis and treatment monitoring of EPTB. Between 2012 and 2017, 734 EPTB patients were diagnosed and recruited from Tongji hospital, and 1,137 suspected EPTB patients who had other diagnoses were recruited as non-EPTB controls. To validate the study, another small group of EPTB patients and non-EPTB controls were recruited from Sino-French New City Branch of Tongji Hospital. The positive rate of peripheral blood T-SPOT in EPTB and non-EPTB were 88.15 and 32.28%. In T-SPOT positive patients, the direct T-SPOT results had limited value in distinguishing these two conditions. A further calculation of the TBAg/PHA ratio of T-SPOT showed improved performance in each form of EPTB. If using 0.20 as the threshold value of the TBAg/PHA ratio, the pooled sensitivity and specificity were 70.79 and 91.55% in distinguishing EPTB from non-EPTB. The validation results showed a better performance of the TBAg/PHA ratio in distinguishing these two conditions, with a sensitivity and specificity of 81.82 and 97.56%, respectively. Comparing with directly using T-SPOT results, the TBAg/PHA ratio was less affected by immunosuppression. Furthermore, PHA value reflected immunosuppression and could help to judge the credibility of T-SPOT results in EPTB patients with different immune status. The TBAg/PHA ratio was significantly decreased during anti-tuberculosis (TB) treatment, which suggests that it can also be used to monitor therapeutic efficacy. These data provide new insights into the role of T-SPOT assay in TB disease, and the TBAg/PHA ratio might be a useful tool for diagnosis and treatment monitoring of EPTB.

近年来，肺外结核（Extrapulmonary tuberculosis, EPTB）的发病率呈上升趋势，但其诊断仍为临床一大难题。本研究分析了结核感染T细胞检测（T-SPOT.TB, T-SPOT）中，结核特异性抗原（TB-specific antigen, TBAg）与植物血凝素（phytohemagglutinin, PHA）的比值（TBAg/PHA比值）在肺外结核诊断与治疗监测中的应用价值。2012年至2017年间，研究团队从同济医院纳入734例确诊肺外结核患者，同时招募1137例确诊为其他疾病的疑似肺外结核患者作为非肺外结核对照。为验证本研究结论，另从同济医院中法新城院区纳入小样本的肺外结核患者与非肺外结核对照队列。肺外结核组与非肺外结核对照组的外周血T-SPOT阳性率分别为88.15%与32.28%。在T-SPOT检测呈阳性的患者中，直接采用T-SPOT结果鉴别两类人群的价值有限。进一步计算T-SPOT的TBAg/PHA比值后，其在各型肺外结核中的鉴别性能得到显著提升。若以0.20作为TBAg/PHA比值的截断值，其区分肺外结核与非肺外结核受试者的合并灵敏度为70.79%，合并特异度为91.55%。验证队列结果显示，TBAg/PHA比值的鉴别性能更优，灵敏度与特异度分别达81.82%与97.56%。相较于直接使用T-SPOT检测结果，TBAg/PHA比值受免疫抑制状态的影响更小。此外，PHA值可反映机体免疫抑制程度，有助于判断不同免疫状态下肺外结核患者T-SPOT检测结果的可信度。抗结核（TB）治疗期间，TBAg/PHA比值会显著降低，提示该指标可用于肺外结核的治疗疗效监测。本研究数据为结核感染T细胞检测在结核病诊疗中的应用提供了新的研究视角，TBAg/PHA比值有望成为肺外结核诊断与治疗监测的有效工具。