Multiple cytokines for the detection of <i>Mycobacterium tuberculosis</i> infection in children with tuberculosis

Nausch, Norman; Lundtoft, Christian; Schulz, Gabriele; Henckel, Hanns-Benjamin; Mayatepek, Ertan; Fleischer, Bernhard; Marx, Florian M.; Jacobsen, Marc

doi:10.5588/ijtld.16.0351

Cited by 22 publications

(26 citation statements)

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“…Whereas others confirmed the capability of IL-6 to detect M. tuberculosis in contacts of tuberculosis patients [28], own previous studies indicated a minor capacity of IL-6 in a tuberculosis low-endemic region [22]. IP-10, a potential biomarker described to improve sensitivity of IGRAs especially in children [16,29] and in HIV co-infection [30,31] detected low proportions of particularly HIV co-infected children.…”

Section: Discussionmentioning

confidence: 87%

“…In addition, we recently performed a pilot study in Germany of children with TB, latent M. tuberculosis infection, and noninfected controls [22]. This study showed highly concordant results between ELISA-and CBA-based IFN-γ measurements.…”

Section: Discussionmentioning

confidence: 88%

“…Examples for indeterminate tests because of high IFN-γ background values are rarely described [33]. Since CBA results were found to be highly concordant to results obtained by ELISA [22], we predicted that 36 individuals (73%) had indeterminate test results based on the QFT ELISA criteria, and this was due to high IFN-γ background levels in the vast majority (n = 35) of children.…”

Section: Discussionmentioning

confidence: 97%

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Alternative Quantiferon cytokines for diagnosis of children with active tuberculosis and HIV co-infection in Ghana

Lundtoft

Awuah

Nausch

et al. 2017

Med Microbiol Immunol

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IFN-γ release assays (IGRAs) often present false-negative or indeterminate results in children with tuberculosis. HIV co-infection may contribute to decreased sensitivity of IGRAs by impairing T-cell IFN-γ expression. Measurement of alternative cytokines in QuantiFERON (QFT) supernatants can circumvent the IFN-γ-dependency and may improve QFT sensitivity. We aimed to identify additional cytokines from QFT supernatants for detection of Mycobacterium tuberculosis infection in children with tuberculosis and HIV co-infection from Ghana. Concentrations of 18 cytokines in QFT supernatants from children (0-16 years) with tuberculosis concomitantly infected with HIV (n = 25) or without HIV (n = 24) from Ghana were measured using cytometric bead array (CBA). 29% of the children showed positive IFN-γ test results, and five cytokines, i.e., IL-6, IL-21, TNF-α, IL-1α and IP-10, detected M. tuberculosis infection with comparable or, for IL-6, with significantly higher sensitivity (59%). Increased age and HIV co-infection were associated with decreased cytokine induction, and especially IL-21 and IP-10 were less prevalent in HIV co-infected children with tuberculosis. Combined cytokine analyses increased proportions of positive tests, and a four-cytokine subset (i.e., IL-6, IL-21, IFN-γ, IL-1α) predicted 78% of the children with tuberculosis correctly. Combined evaluation of IFN-γ and alternative cytokines improved IGRA-sensitivity in children with tuberculosis.

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 97%

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Alternative Quantiferon cytokines for diagnosis of children with active tuberculosis and HIV co-infection in Ghana

Lundtoft

Awuah

Nausch

et al. 2017

Med Microbiol Immunol

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“…There is a long list of articles describing the increased production of TNF-α during LTBI [12][13][14][15][16]. Therefore, the choice of its measurement as a marker for the laboratory diagnosis of LTBI seems to be relevant.…”

Section: Discussionmentioning

confidence: 99%

“…However, it is also true that there are new efforts to identify the potential biomarkers from the supernatants of samples of IGRA test. It became apparent from these studies that among the great number of newly identified compounds and the "classic" biomarker (IFN γ), tumour necrosis alpha (TNF-α) was always detectable as one of the key molecules for Mycobacterial dormancy and host responses in tuberculosis [12][13][14][15][16].…”

Section: Research Articlementioning

confidence: 99%

Index of Stimulation and TNFα Measurements Used for laboratory Diagnosis of Latent Tuberculosis as a New Principle

Sipka¹,

Papp²,

Kovács³

et al. 2018

IJPID

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A new principle of a method for the laboratory diagnosis of latent Mycobacterium tuberculosis infection (LBTI) compared to the QuantiFERON (QFT) test is presented. The new elements, the calculation and introduction of an Index of Stimulation (IS) were based on the measurements of tumour necrosis-α (TNF-α) release in whole human blood stimulated by the peptides (TB-P) derived from Mycobacterium tuberculosis (Mtb) related proteins and Purified Protein Derivative (PPD). The amount of TNF-α was determined by ELISA. The calculation of IS values was carried by the formula: TNFα(pg/ml)TB-P/ TNF-α(pg/ml)PPD. The populations studied consisted of a) 15 healthcare workers dealing with Mtb-infected patients (HCW-TB); b) 14 healthcare workers not being exposed to Mtb patients (HCW-C) as controls. The diagnosis of LTBI was established if IS was higher than 1.50. In the HCW-TB group the number of LTBI was 6/15 by the new method and 9/15 by QFT. Tested clinically, the number of false-positive results by QFT was 3/9. All members of HCW-C group were LTBI negative by both methods. This new assay did not result in any false positive reactions. Although these results are still preliminary data derived from few patients. However, the theoretical novelties in the principle of method: the calculation of IS from the TNF-α-TB-P/ TNF-α-PPD values can mean a progress in the individual laboratory diagnosis of LTBI in further studies.

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Impaired T-cell response to phytohemagglutinin (PHA) in tuberculosis patients is associated with high IL-6 plasma levels and normalizes early during anti-mycobacterial treatment

et al. 2023

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Purpose Human tuberculosis is characterized by immunopathology that affects T-cell phenotype and functions. Previous studies found impaired T-cell response to phytohemagglutinin (PHA) in patients with acute tuberculosis. However, the influence of disease severity, affected T-cell subsets, and underlying mechanisms remain elusive. Methods Here we investigated PHA-induced and antigen-specific T-cell effector cytokines in tuberculosis patients (n = 55) as well as in healthy asymptomatic contacts (n = 32) from Ghana. Effects of Mycobacterium (M.) tuberculosis sputum burden and treatment response were analyzed and compared during follow-up. Finally, cytokine characteristics of the aberrant plasma milieu in tuberculosis were analyzed as a potential cause for impaired PHA response. Results PHA-induced IFN-γ expression was significantly lower in sputum-positive tuberculosis patients as compared to both, contacts and paucibacillary cases, and efficiently discriminated the study groups. T-cell responses to PHA increased significantly early during treatment and this was more pronounced in tuberculosis patients with rapid treatment response. Analysis of alternative cytokines revealed distinct patterns and IL-22, as well as IL-10, showed comparable expression to IFN-γ in response to PHA. Finally, we found that high IL-6 plasma levels were strongly associated with impaired IFN-γ and IL-22 response to PHA. Conclusion We conclude that impaired T-cell response to PHA stimulation in acute tuberculosis patients (i) was potentially caused by the aberrant plasma milieu, (ii) affected differentially polarized T-cell subsets, (iii) normalized early during treatment. This study shed light on the mechanisms of impaired T-cell functions in tuberculosis and yielded promising biomarker candidates for diagnosis and monitoring of treatment response.

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Multiple cytokines for the detection of Mycobacterium tuberculosis infection in children with tuberculosis

Abstract: Our results did not suggest that alternative IGRA cytokines can distinguish between children with active TB and those with LTBI. IFN-γ and IL-2 showed comparable capacity in diagnosing M. tuberculosis infection in our study groups.

Cited by 22 publications

References 0 publications

Alternative Quantiferon cytokines for diagnosis of children with active tuberculosis and HIV co-infection in Ghana

Alternative Quantiferon cytokines for diagnosis of children with active tuberculosis and HIV co-infection in Ghana

Index of Stimulation and TNFα Measurements Used for laboratory Diagnosis of Latent Tuberculosis as a New Principle

Impaired T-cell response to phytohemagglutinin (PHA) in tuberculosis patients is associated with high IL-6 plasma levels and normalizes early during anti-mycobacterial treatment

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