Sester Martina, Sester Urban, Clauer Peter, Heine Gunnar, Mack Ulrich, Moll Thomas, Sybrecht Gerhard W, Lalvani Ajit, Köhler Hans
Medical Department IV, University of the Saarland, Homburg, Germany.
Kidney Int. 2004 May;65(5):1826-34. doi: 10.1111/j.1523-1755.2004.00586.x.
Identification of latent Mycobacterium tuberculosis infection in hemodialysis patients is hampered by reduced sensitivity of the established tuberculin skin test. We investigated whether in vitro quantitation of purified protein derivative (PPD)-specific T cells using a rapid 6-hour assay may represent an alternative approach for detecting latent infection.
One hundred and twenty-seven hemodialysis patients and 218 control patients (blood donors, health care workers, and control patients) were analyzed. Specific T cells toward PPD and early secretory antigenic target-6 (ESAT-6), a protein expressed in Mycobacterium tuberculosis but absent from M. bovis bacillus Calmette-Guerin (BCG) vaccine strains, were flow cytometrically quantified from whole blood, and results were compared with skin testing.
Compared to blood donors, a high proportion of both health care workers (48.6%) and hemodialysis patients (53.5%) had PPD-specific Th1-type CD4 T-cell reactivity with similar median frequencies of PPD-specific T cells (0.17%; 0.06-3.75% vs. 0.26%; 0.06-4.12%, respectively). In contrast, skin test reactivity was significantly reduced in hemodialysis patients. Whereas 85.7% of control patients with PPD reactivity in vitro were skin test-positive, the respective percentage among hemodialysis patients was 51.4% (P= 0.007). Among individuals with PPD reactivity in vitro, approximately 50% had T cells specific for ESAT-6.
Unlike the skin test, measurement of PPD reactivity by in vitro quantitation of PPD-specific T cells was unaffected by uremia-associated immunosuppression. This whole-blood assay may thus be a valuable alternative to skin testing, and detection of ESAT-6-specific T cells could moreover allow distinction of latent M. tuberculosis infection from BCG-induced reactivity to PPD. The assay is well suited for clinical use and may facilitate targeting of preventative therapy in high-risk individuals.
已确立的结核菌素皮肤试验敏感性降低，阻碍了血液透析患者中潜伏性结核分枝杆菌感染的识别。我们研究了使用快速6小时检测法对纯化蛋白衍生物（PPD）特异性T细胞进行体外定量是否可能代表一种检测潜伏感染的替代方法。
分析了127例血液透析患者和218例对照患者（献血者、医护人员和对照患者）。通过流式细胞术从全血中定量针对PPD和早期分泌性抗原靶标6（ESAT-6）的特异性T细胞，ESAT-6是一种在结核分枝杆菌中表达但卡介苗（BCG）疫苗株中不存在的蛋白质，并将结果与皮肤试验进行比较。
与献血者相比，医护人员（48.6%）和血液透析患者（53.5%）中很大一部分人具有PPD特异性Th1型CD4 T细胞反应性，PPD特异性T细胞的中位频率相似（分别为0.17%；0.06 - 3.75%和0.26%；0.06 - 4.12%）。相比之下，血液透析患者的皮肤试验反应性显著降低。体外具有PPD反应性的对照患者中85.7%皮肤试验呈阳性，而血液透析患者中的相应百分比为51.4%（P = 0.007）。在体外具有PPD反应性的个体中，约50%具有针对ESAT-6的T细胞。
与皮肤试验不同，通过体外定量PPD特异性T细胞来测量PPD反应性不受尿毒症相关免疫抑制的影响。因此，这种全血检测可能是皮肤试验的一种有价值的替代方法，而且检测ESAT-6特异性T细胞可以区分潜伏性结核分枝杆菌感染与卡介苗诱导的对PPD的反应性。该检测非常适合临床使用，可能有助于在高危个体中针对性地进行预防性治疗。
