Department of Research and Development, Queen Saovabha Memorial Institute, Thai Red Cross Society, Bangkok 10330, Thailand.
J Med Microbiol. 2019 Sep;68(9):1314-1319. doi: 10.1099/jmm.0.001037.
Current intradermal tuberculin skin tests for latent tuberculosis infection (LTBI) based on purified protein derivative (PPD) have poor specificity. Developing a better skin test antigen as well as a simple skin patch test may improve and facilitate diagnostic performance. Defined recombinant antigens that were unique to (MTB), including two potential latency-associated antigens (ESAT-6 and Rv2653c) and five DosR-encoded latency proteins (Rv1996, Rv2031c, Rv2032, DevR and Rv3716c), were used as diagnostic skin test reagents in comparison with a standard PPD. The performance of the skin tests based on the detection of delayed-type hypersensitivity (DTH) reaction in guinea pigs sensitized to MTB and bacille Calmette-Guérin (BCG) vaccine was evaluated. The latency antigens Rv1996, Rv2031c, Rv2032 and Rv2653c and the ESAT-6 protein elicited less reactive DTH skin responses in MTB-sensitized guinea pigs than those resulting from PPD, but elicited no response in BCG-vaccinated guinea pigs. The remaining two latency antigens (DevR and Rv3716c) elicited DTH responses in both groups of animals, as did PPD. The reactivity of PPD in BCG-vaccinated guinea pigs was greater than that of any of the selected skin test reagents. Using stronger concentrations of selected skin test reagents in the patch test led to increased DTH responses that were comparable to those elicited by PPD in guinea pigs sensitized with MTB. Transdermal application of defined purified antigens might be a promising method for LTBI screening.
目前基于纯化蛋白衍生物(PPD)的皮内结核菌素皮肤试验(TST)对潜伏性结核感染(LTBI)的特异性较差。开发更好的皮肤试验抗原以及简单的皮肤贴剂试验可能会改善和促进诊断性能。使用定义的、针对 MTB 的独特重组抗原,包括两种潜在的潜伏相关抗原(ESAT-6 和 Rv2653c)和五种 DosR 编码的潜伏蛋白(Rv1996、Rv2031c、Rv2032、DevR 和 Rv3716c),与标准 PPD 进行比较,作为诊断皮肤试验试剂。评估了基于豚鼠对 MTB 和卡介苗(BCG)疫苗致敏后迟发型超敏反应(DTH)反应检测的皮肤试验性能。与 PPD 相比,潜伏抗原 Rv1996、Rv2031c、Rv2032 和 Rv2653c 以及 ESAT-6 蛋白在 MTB 致敏豚鼠中引起的 DTH 皮肤反应较弱,但在 BCG 接种豚鼠中没有引起反应。其余两种潜伏抗原(DevR 和 Rv3716c)在两组动物中均引起 DTH 反应,与 PPD 相同。BCG 接种豚鼠中 PPD 的反应性大于任何选定的皮肤试验试剂。在皮试中使用更强浓度的选定皮肤试验试剂会导致 DTH 反应增加,与 MTB 致敏豚鼠中 PPD 引起的反应相当。经皮应用定义的纯化抗原可能是 LTBI 筛查的一种有前途的方法。