Rangaka Molebogeng X, Diwakar Lavanya, Seldon Ronnett, van Cutsem Gilles, Meintjes Graeme A, Morroni Chelsea, Mouton Priscilla, Shey Muki S, Maartens Gary, Wilkinson Katalin A, Wilkinson Robert J
Institute of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
Clin Infect Dis. 2007 Jun 15;44(12):1639-46. doi: 10.1086/518234. Epub 2007 May 10.
Human immunodeficiency virus (HIV)-associated tuberculosis is a major cause of mortality in Africa. The assay of T cell interferon- gamma released in response to antigens of greater specificity than purified protein derivative is a useful improvement over the Mantoux tuberculin skin test, but few studies have evaluated interferon-gamma secretion in HIV-infected individuals.
Mycobacterium tuberculosis antigen-specific interferon-gamma secretion was assessed by whole blood assay and enzyme-linked immunospot, which were compared with the Mantoux tuberculin skin test in HIV-infected and HIV-uninfected individuals without active tuberculosis and HIV-infected patients with pulmonary tuberculosis in Khayelitsha, South Africa.
The skin test and whole blood assay responses to purified protein derivative in HIV-positive subjects were decreased, compared with responses in HIV-negative subjects (P < .001). By contrast, the responses to M. tuberculosis antigens (early secreted antigenic target 6, culture filtrate protein 10, TB10.3, and alpha-crystallin 2) were less affected, indicating a high prevalence of latent tuberculosis (approximately 80%) in both HIV-negative and HIV-positive subject groups. Whole blood assay responses did not differ between the HIV-positive subjects without tuberculosis and HIV-positive subjects with tuberculosis, but the enzyme-linked immunospot method response to early secreted antigenic target 6 and culture filtrate protein 10 was higher in the group of HIV-infected subjects with tuberculosis (P < or = .04), although this group had lower CD4+ cell counts. A ratio of the combined enzyme-linked immunospot method response divided by the CD4+ cell count of > 1.0 had 88% sensitivity and 80% specificity for active pulmonary tuberculosis in HIV-infected individuals.
Interferon-gamma release appears to be less impaired than skin testing by HIV coinfection. The novel potential to relate the enzyme-linked immunospot method and CD4+ cell count to assist diagnosis of active tuberculosis in patients with HIV infection is important and deserves further evaluation.
人类免疫缺陷病毒（HIV）相关结核病是非洲主要的死亡原因。与纯化蛋白衍生物相比，针对更具特异性抗原的T细胞γ干扰素释放检测是对结核菌素皮肤试验的一项有益改进，但很少有研究评估HIV感染者的γ干扰素分泌情况。
采用全血检测和酶联免疫斑点法评估结核分枝杆菌抗原特异性γ干扰素分泌，并将其与南非开普敦Khayelitsha地区未患活动性结核病的HIV感染者和未感染HIV个体以及患肺结核的HIV感染者的结核菌素皮肤试验结果进行比较。
与HIV阴性受试者相比，HIV阳性受试者对纯化蛋白衍生物的皮肤试验和全血检测反应降低（P <.001）。相比之下，对结核分枝杆菌抗原（早期分泌性抗原靶6、培养滤液蛋白10、TB10.3和α晶状体蛋白2）的反应受影响较小，表明HIV阴性和HIV阳性受试者组中潜伏性结核的患病率均较高（约80%）。未患结核病的HIV阳性受试者和患结核病的HIV阳性受试者的全血检测反应无差异，但酶联免疫斑点法对早期分泌性抗原靶6和培养滤液蛋白10的反应在患结核病的HIV感染受试者组中更高（P ≤.04），尽管该组CD4+细胞计数较低。酶联免疫斑点法反应与CD4+细胞计数之比>1.0时，对HIV感染个体活动性肺结核的诊断敏感性为88%，特异性为80%。
γ干扰素释放似乎比HIV合并感染对皮肤试验的损害更小。将酶联免疫斑点法与CD4+细胞计数相关联以辅助诊断HIV感染患者活动性结核病的新潜力很重要，值得进一步评估。
