Assessment of the novel T-cell activation marker–tuberculosis assay for diagnosis of active tuberculosis in children: a prospective proof-of-concept study

Portevin, Damien; Moukambi, Félicien; Clowes, Petra; Bauer, Asli; Chachage, Mkunde; Ntinginya, Nyanda Elias; Mfinanga, Elirehema; Said, Khadija; Haraka, Frederick; Rachow, Andrea; Saathoff, Elmar; Mpina, Maximilian; Jugheli, Levan; Lwilla, Fred; Marais, Ben J.; Höelscher, Michael; Daubenberger, Claudia; Reither, Klaus; Geldmacher, Christof

doi:10.1016/s1473-3099(14)70884-9

Cited by 122 publications

(136 citation statements)

References 28 publications

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“…Other studies evaluated frequencies of single and polyfunctional cytokine-producing Mtb-specific T (28, 43). Expression of the costimulatory molecule CD27 on Mtb-specific T cells was recently shown to have predictive value in distinguishing active and latent TB; however, CD27 + IFN-γ + CD4 + T cell frequencies were not evaluated in the context of monitoring treatment response in longitudinal studies (44)(45)(46).…”

Section: Cd4mentioning

confidence: 99%

Biomarkers on patient T cells diagnose active tuberculosis and monitor treatment response

Adékambi¹,

Ibegbu²,

Cagle³

et al. 2015

J. Clin. Invest.

140

189

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Section: Cd4mentioning

confidence: 99%

Biomarkers on patient T cells diagnose active tuberculosis and monitor treatment response

Adékambi¹,

Ibegbu²,

Cagle³

et al. 2015

J. Clin. Invest.

140

189

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“…Moreover, our results were achieved irrespective of Mtb culture status, and although greater sensitivity was achieved in culture-positive samples, results from culture-negative samples markedly outperformed the WHO-defined 66% optimal sensitivity for new high-priority nonsputum diagnostic tests (13). NanoDisk-MS also accurately diagnosed active TB cases in patients with HIV coinfection, which can adversely skew the results of blood-based host response immunoassays (e.g., IGRA and T-cell activation marker-tuberculosis assay) (26,36), in which serum Mtb peptide concentrations were found to equal or exceed those found in HIV-negative subjects, supporting robust assay sensitivity. NanoDisk-MS exhibited differential specificities with healthy (100%) and HIV-positive (89.7%) controls, LTBI cases (87.1%), and NTM cases (90.6%), however.…”

Section: Discussionmentioning

confidence: 94%

“…Noninvasive diagnosis of EPTB is challenging owing to the paucibacillary nature of patient sputum samples, and thus Mtb cultures are often done using more invasive specimens, including lymph nodes and pleural or cerebrospinal fluid. EPTB is particularly common in HIV/TB-coinfected patients, and HIV infection can disrupt pulmonary granulomas, which may reduce the utility of sputum-based diagnostic tests, whereas the altered immune responses in these patients may limit the utility of T-cell-mediated diagnostic assays (26). We analyzed serum samples from HIV-positive HTI subjects with culture-positive or -negative PTB or EPTB.…”

Section: Nanodisk-ms Diagnostic Sensitivity and Specificity In An Hivmentioning

confidence: 99%

Quantification of circulating Mycobacterium tuberculosis antigen peptides allows rapid diagnosis of active disease and treatment monitoring

Liu

Zhao

Fan

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Tuberculosis (TB) is a major global health threat, resulting in an urgent unmet need for a rapid, non-sputum-based quantitative test to detect active Mycobacterium tuberculosis (Mtb) infections in clinically diverse populations and quickly assess Mtb treatment responses for emerging drug-resistant strains. We have identified Mtb-specific peptide fragments and developed a method to rapidly quantify their serum concentrations, using antibody-labeled and energy-focusing porous discoidal silicon nanoparticles (nanodisks) and high-throughput mass spectrometry (MS) to enhance sensitivity and specificity. NanoDisk-MS diagnosed active Mtb cases with high sensitivity and specificity in a case-control study with cohorts reflecting the complexity of clinical practice. Similar robust sensitivities were obtained for cases of culture-positive pulmonary TB (PTB; 91.3%) and extrapulmonary TB (EPTB; 92.3%), and the sensitivities obtained for culture-negative PTB (82.4%) and EPTB (75.0%) in HIV-positive patients significantly outperformed those reported for other available assays. NanoDisk-MS also exhibited high specificity (87.1-100%) in both healthy and high-risk groups. Absolute quantification of serum Mtb antigen concentration was informative in assessing responses to antimycobacterial treatment. Thus, a NanoDisk-MS assay approach could significantly improve the diagnosis and management of active TB cases, and perhaps other infectious diseases as well.D espite international efforts and initiatives, tuberculosis (TB) remains a major public health concern worldwide, associated with high morbidity and mortality (1, 2). Detecting active TB cases and monitoring their responses to therapy are fraught with challenges, relying predominantly on microbiologic techniques that use sputum samples, including acid-fast Bacillus (AFB) smear microscopy-widely used as an initial test for TB diagnosis (3, 4)-and Mycobacterium tuberculosis (Mtb) culture, both of which have only moderate sensitivity and specificity and a long turnaround time (5, 6). Moreover, sputum samples are difficult to obtain after symptom improvement, and often are not diagnostically useful for extrapulmonary TB (EPTB) cases. The PCR-based Xpert MTB/RIF sputum assay was introduced to improve the speed and specificity of TB diagnosis, but this assay has poor sensitivity under low bacterial loads and cannot distinguish live and nonviable Mtb contributions (7,8). A recent World Health Organization (WHO) policy update acknowledged the low quality of evidence supporting the use of Xpert MTB/RIF to diagnose EPTB (9). Diagnostic challenges can be further magnified in patients coinfected with HIV and TB (10). In addition, none of these techniques provides quantitative results that can be used to monitor treatment effects (11,12).Consequently, there is an urgent need, highlighted as a high priority in a recent WHO consensus report (13), for the development of rapid, quantitative, non-sputum-based biomarker tests that do not require bacterial isolation to detect active TB (13). Non-s...

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“…Recently, a new assay, the T-cell activation marker of TB (TAM-TB), has been proposed. 39 Different from the other approaches, it evaluates the ratio of the median fluorescence intensity (MFI) of CD27 within the CD4 þ T-cells over the MFI of CD27 in the Mtbspecific CD4 T-cells. 39 The TAM-TB assay differentiates active TB from LTBI in children.…”

Section: Introductionmentioning

confidence: 99%

“…39 Different from the other approaches, it evaluates the ratio of the median fluorescence intensity (MFI) of CD27 within the CD4 þ T-cells over the MFI of CD27 in the Mtbspecific CD4 T-cells. 39 The TAM-TB assay differentiates active TB from LTBI in children. 39 In the present study, we used several concomitant approaches to evaluate whether detection of the CD27 surface expression on Mtb specific-CD4 þ T-cells is a useful marker to discriminate active disease from LTBI in adult individuals from a low TB-endemic country such as Italy.…”

Section: Introductionmentioning

confidence: 99%

Assessment of CD27 expression as a tool for active and latent tuberculosis diagnosis

Petruccioli

Petrone

Vanini

et al. 2015

Journal of Infection

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Assessment of the novel T-cell activation marker–tuberculosis assay for diagnosis of active tuberculosis in children: a prospective proof-of-concept study

Cited by 122 publications

References 28 publications

Biomarkers on patient T cells diagnose active tuberculosis and monitor treatment response

Biomarkers on patient T cells diagnose active tuberculosis and monitor treatment response

Quantification of circulating Mycobacterium tuberculosis antigen peptides allows rapid diagnosis of active disease and treatment monitoring

Assessment of CD27 expression as a tool for active and latent tuberculosis diagnosis

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