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Use of the T-spot.TB test for the diagnosis of latent tuberculosis infection

机译:使用T-spot.TB测试诊断潜伏性结核感染

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Background:Tuberculosis (TB) represents a major health problem both in developing and both in industrialized countries.The identification of individuals latently infected with Mycobacterium tuberculosis (Mtb) play a key role for the efficacy of TB control. These individuals with a latent tuberculosis infection (LTBI), especially those with high risk of reactivation (e.g. HIV + / AIDS-infected individuals, patients undergoing immunosuppressive therapy and children younger than 5 years) could benefit from a preventive treatment with isoniazid reducing the risk of progression from LTBI to active TB. Until recently, detection of LTBI has relied on the tuberculin skin test (TST), but despite the widespread use in clinical practice,TST does not reliably diagnose LTBI because several drawbacks, e.g. lacking in specificity, particularly in who were exposed to non-tuberculous mycobacteria (NTM) or were vaccinated with Bacille Calmette-Guerin (BCG) In addition, in young subjects,TST sensitivity is hampered by impaired T cell function leading frequently to false negative results.These several drawbacks limit the use of TST for the diagnose an LTBI in patients who may benefit from preventive chemotherapy. On the other hand, an accurate diagnosis of LTBI avoid the over-treatment of those patients with a positive TST results but not latently infected with Mtb. Recently, new tests based on the detection of interferon-gamma (IFN-γ) after stimulation with Mtb-specific antigens: Early secretory Antigenic Target-6 (ESAT-6) and Culture Filtrate Protein-10 (CFP-10) have been proposed for the diagnosis of active TB and LTBI. Methods: During the period from January 2009 to June 2009, in our laboratory 70 patients were tested with T-SPOT.TB (Oxford Immunotech, Abingdon, United Kingdom).We enrolled transplant patients and subjects ongoing transplant, patients immigrants from high prevalence TB countries, patients screened for immunosuppressive treatment, HIV / AIDS – infected individuals.We also tested 3 patients with clinical / radiological suspicion of active TB and 3 patients with positive tuberculin skin test and with a positive direct examination for mycobacteria in the urinary sediment. Results: In 2 patients with symptoms suggestive of TB in place,T-SPOT.TB showed a higher response of (IFN-g), more than 100 spots.Among individuals ongoing renal transplant, 6 patients tested T-SPOT.TB positive and 4 subjects were T.SPOT.TB -negative. Two patients with an autoimmune disease showed an high response to Mtb-specific antigens with T-SPOT.TB test tested before to start any treatment.T-SPOT.TB test tested strongly negative in 4 paediatric patients and in one HIV-infected individuals, regardless a positive response to a internal positive response (phytohaemagglutinin (PHA), suggesting a normal immune response. Conclusions:This preliminary data suggest that the T.SPOT.TB showed high sensitivity and specificity, producing a strongly negative response to Mtb-specific antigens in subjects who had a history of previous BCG-vaccination. In addition, T-SPOT.TB test provides, unlike the TST, indication about the potential immunosuppression of tested patient with an internal positive control that can highlight the production of IFN- γ by lymphocytes resulting in the application of this test in immunocompromised patients, e.g. children and transplantated patients and others.
机译:背景:结核病(TB)在发展中国家和工业化国家都代表着主要的健康问题。潜伏感染结核分枝杆菌(Mtb)的个体的鉴定对于控制结核病的有效性起着关键作用。这些具有潜伏性结核感染(LTBI)的个体,尤其是那些具有高再激活风险的个体(例如,感染HIV + / AIDS的个体,接受免疫抑制治疗的患者以及5岁以下的儿童)可以从异烟肼的预防性治疗中受益,从而降低风险从LTBI到活动性TB的进展。直到最近,LTBI的检测还依赖于结核菌素皮肤试验(TST),但尽管在临床实践中得到了广泛的应用,TST仍不能可靠地诊断LTBI,因为它存在一些缺点,例如,缺乏特异性,尤其是那些暴露于非结核分枝杆菌(NTM)或接种了卡介苗的细菌(BCG)。此外,在年轻受试者中,T细胞功能受损会阻碍TST敏感性,经常导致假阴性结果这几个缺点限制了使用TST诊断可能从预防性化疗获益的患者的LTBI。另一方面,LTBI的准确诊断可避免对那些TST结果阳性但未潜伏感染Mtb的患者进行过度治疗。最近,已经提出了基于检测Mtb特异性抗原后干扰素-γ(IFN-γ)的新测试:早期分泌性抗原靶标6(ESAT-6)和培养滤液蛋白10(CFP-10)。用于活动性结核病和LTBI的诊断。方法:2009年1月至2009年6月,在我们的实验室中对70例T-SPOT.TB(Oxford Immunotech,Abingdon,United Kingdom)的患者进行了测试,我们纳入了移植患者和正在进行移植的患者,这些患者来自高流行性结核病在一些国家/地区,对接受过免疫抑制治疗,HIV / AIDS感染者进行了筛查。我们还对3名临床/放射学怀疑活动性结核病患者和3例结核菌素皮肤试验阳性且尿沉渣中分枝杆菌阳性的患者进行了检测。结果:在2例提示存在TB症状的患者中,T-SPOT.TB表现出更高的(IFN-g)反应,超过100个斑点。在正在进行肾脏移植的个体中,有6例患者检测了T-SPOT.TB阳性和4名受试者为T.SPOT.TB阴性。在开始任何治疗之前,通过T-SPOT.TB测试对两名自身免疫性疾病患者表现出对Mtb特异性抗原的高响应。在4名儿科患者和1名受HIV感染的个体中,T-SPOT.TB测试均呈强烈阴性,结论:该初步数据表明,T.SPOT.TB表现出高度的敏感性和特异性,对Mtb特异性抗原产生强烈的阴性反应,无论对内部阳性反应(植物血凝素(PHA)的阳性反应),都表明免疫反应正常。此外,与TST不同,T-SPOT.TB测试可提供受试患者具有内部阳性对照的潜在免疫抑制作用的迹象,该内部阳性对照可突出显示BCG疫苗的产生。淋巴细胞导致该测试在免疫功能低下的患者(例如儿童,移植患者和其他患者)中的应用。

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