Dominant TNF-α+ Mycobacterium tuberculosis-specific CD4+ T cell responses discriminate between latent infection and active disease

被引：327

作者：

Harari, Alexandre ^{[1
,2
]}

Rozot, Virginie ^{[1
]}

Enders, Felicitas Bellutti ^{[1
]}

Perreau, Matthieu ^{[1
]}

Stalder, Jesica Mazza ^{[3
]}

Nicod, Laurent P. ^{[3
]}

Cavassini, Matthias ^{[4
]}

Calandra, Thierry ^{[4
]}

Blanchet, Catherine Lazor ^{[5
]}

Jaton, Katia ^{[6
]}

Faouzi, Mohamed ^{[7
]}

Day, Cheryl L. ^{[8
]}

Hanekom, Willem A. ^{[8
]}

Bart, Pierre-Alexandre ^{[1
]}

Pantaleo, Giuseppe ^{[1
,2
]}

机构：

[1] Univ Lausanne, Div Immunol & Allergy, CHU Vaudois, Lausanne, Switzerland

[2] Swiss Vaccine Res Inst, Lausanne, Switzerland

[3] Univ Lausanne, Div Pneumol, CHU Vaudois, Lausanne, Switzerland

[4] Univ Lausanne, Div Infect Dis, CHU Vaudois, Lausanne, Switzerland

[5] Univ Lausanne, Div Occupat Med, CHU Vaudois, Lausanne, Switzerland

[6] Univ Lausanne, Inst Microbiol, CHU Vaudois, Lausanne, Switzerland

[7] Univ Lausanne, Ctr Clin Epidemiol, CHU Vaudois, Lausanne, Switzerland

[8] Univ Cape Town, S African TB Vaccine Initiat, ZA-7925 Cape Town, South Africa

来源：

NATURE MEDICINE | 2011年 / 17卷 / 03期

基金：

比尔及梅琳达.盖茨基金会;

关键词：

NECROSIS-FACTOR-ALPHA; FUNCTIONAL SIGNATURES; RHEUMATOID-ARTHRITIS; IMMUNOLOGY; DIAGNOSIS; IMMUNITY; ASSAY;

D O I：

10.1038/nm.2299

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Rapid diagnosis of active Mycobacterium tuberculosis (Mtb) infection remains a clinical and laboratory challenge. We have analyzed the cytokine profile (interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) and interleukin-2 (IL-2)) of Mtb-specific T cells by polychromatic flow cytometry. We studied Mtb-specific CD4(+) T cell responses in subjects with latent Mtb infection and active tuberculosis disease. The results showed substantial increase in the proportion of single-positive TNF-alpha Mtb-specific CD4(+) T cells in subjects with active disease, and this parameter was the strongest predictor of diagnosis of active disease versus latent infection. We validated the use of this parameter in a cohort of 101 subjects with tuberculosis diagnosis unknown to the investigator. The sensitivity and specificity of the flow cytometry-based assay were 67% and 92%, respectively, the positive predictive value was 80% and the negative predictive value was 92.4%. Therefore, the proportion of single-positive TNF-alpha Mtb-specific CD4(+) T cells is a new tool for the rapid diagnosis of active tuberculosis disease.

引用

页码：372 / U174

页数：6

共 22 条

[1] An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis [J].