Rapid detection of Mycobacterium tuberculosis infection by enumeration of antigen-specific T cells

Rapid detection of Mycobacterium tuberculosis infection by enumeration of antigen-specific T cells
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DOI:
10.1164/ajrccm.163.4.2009100
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发表时间:
2001-03-01
影响因子:
24.7
通讯作者:
Hill, AVS
Hill, AVS
中科院分区:
医学1区
文献类型:
--
作者:
Lalvani, A;Pathan, AA;Hill, AVS

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没有可靠的方法来检测潜在的M。肺结核感染,甚至在活动性肺结核患者中,感染往往未经证实。我们假设M。结核抗原特异性T细胞可能可靠地指示感染。我们列举了外周血来源的干扰素γ(IFN-γ)分泌T细胞对ESAT-6表位的应答,ESAT-6是一种对M.结核病复杂,但没有BCC,在四组个人。47例细菌学确诊的结核病患者中有45例具有ESAT-6特异性IFN-γ分泌T细胞,而47例非结核病患者中有4例具有ESAT-6特异性IFN-γ分泌T细胞,这表明这些T细胞是M.肺结核感染。因此,该试验检测M的灵敏度为96%(95%置信区间[CI] 92-100)。结核病感染的患者。相比之下,在26例结核病患者中,只有18例(69%)为阳性(p = 0.003)。此外,26名TST阳性暴露的家庭接触者中有22名(85%)具有ESAT-6特异性T细胞,而26名未暴露的BCC疫苗接种受试者中没有反应。这种方法能够快速检测M。在活动性结核病患者和潜伏感染高风险的暴露无症状个体中,它还成功区分了M、结核病感染和BCC疫苗接种。这种能力可能有助于非流行地区的结核病控制。
There is no reliable means of detecting latent M. tuberculosis infection, and even in patients with active tuberculosis, infection is often unconfirmed. We hypothesized that M. tuberculosis antigen-specific T cells might reliably indicate infection. We enumerated peripheral blood-derived interferon gamma (IFN-gamma)-secreting T cells responding to epitopes from ESAT-6, an antigen that is highly specific for M. tuberculosis complex but absent from BCC, in four groups of individuals. Forty-five of 47 patients with bacteriologically confirmed tuberculosis had ESAT-6-specific IFN-gamma -secreting T cells, compared with four of 47 patients with nontuberculous illnesses, indicating that these T cells are an accurate marker of M. tuberculosis infection. This assay thus has a sensitivity of 96% (95% confidence interval [CI] 92-100) for detecting M. tuberculosis infection in this patient population. By comparison, of the 26 patients with tuberculosis who had a diagnostic: tuberculin skin test (TST), only 18 (69%) were positive (p = 0.003). In addition, 22 of 26 (85%) TST-positive exposed household contacts had ESAT-6-specific T cells, whereas zero of 26 unexposed BCC-vaccinated subjects responded. This approach enables rapid detection of M. tuberculosis infection in patients with active tuberculosis and in exposed asymptomatic individuals at high risk of latent infection; it also successfully distinguishes between M, tuberculosis infection and BCC vaccination. This capability may facilitate tuberculosis control in nonendemic regions.