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- Essone, PN, et al.
(author)
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Bifunctional T-cell-derived cytokines for the diagnosis of tuberculosis and treatment monitoring
- 2014
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In: Respiration. - : S. Karger AG. - 1423-0356 .- 0025-7931. ; 88:3, s. 251-261
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Journal article (peer-reviewed)abstract
- <b><i>Background:</i></b> Diagnosis and treatment monitoring of patients with tuberculosis remain challenging. <b><i>Objective:</i></b> We have evaluated whether <i>Mycobacterium</i>-specific interferon (IFN)-γ and interleukin (IL)-2 bifunctional cytokine immune response assays improve the diagnosis of and correlate to treatment response in pulmonary tuberculosis. <b><i>Methods:</i></b> Early secretory antigenic target (ESAT)6/culture filtrate protein 10 (CFP10), microsomal triglyceride transfer protein 65 (MTP65) and the purified protein derivative (PPD) tuberculin-specific immune profiles were investigated in peripheral blood mononuclear cells from 19 patients with culture-confirmed tuberculosis and 23 healthy community controls (HCCs; 82.6% with latent <i>M. tuberculosis</i> infection) using a novel fluorescence-based dual-colour enzyme-linked immunospot (EliSpot) technology (FluoroSpot). <b><i>Results:</i></b> The frequency of ESAT6/CFP10-induced IFN-γ+IL-2- producing cells was elevated (p < 0.001), whereas the percentages of specific IFN-γ-IL-2+ (p = 0.002) and IFN-γ+IL-2+ double producing cells (p = 0.037) were diminished in tuberculosis patients in comparison to HCCs. A 3-host marker model using a combination of those IFN-γ and IL-2 single-cell responses showed 93.8% sensitivity and 77.8% specificity for tuberculosis. During tuberculosis treatment, the PPD-induced immune responses shifted from an IFN-γ+IL-2- dominated profile towards a balance of IFN-γ-IL-2+ and IFN-γ+IL-2+ double producing cells (all p ≤ 0.05). <b><i>Conclusions:</i></b> The addition of antigen-specific IL-2 production to IFN-γ responses by EliSpot in IFN-γ release assays increases diagnostic sensitivity for active tuberculosis.
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- Heyckendorf, J, et al.
(author)
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Prediction of anti-tuberculosis treatment duration based on a 22-gene transcriptomic model
- 2021
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In: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 58:3
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Journal article (peer-reviewed)abstract
- The World Health Organization recommends standardised treatment durations for patients with tuberculosis (TB). We identified and validated a host-RNA signature as a biomarker for individualised therapy durations for patients with drug-susceptible (DS)- and multidrug-resistant (MDR)-TB.MethodsAdult patients with pulmonary TB were prospectively enrolled into five independent cohorts in Germany and Romania. Clinical and microbiological data and whole blood for RNA transcriptomic analysis were collected at pre-defined time points throughout therapy. Treatment outcomes were ascertained by TBnet criteria (6-month culture status/1-year follow-up). A whole-blood RNA therapy-end model was developed in a multistep process involving a machine-learning algorithm to identify hypothetical individual end-of-treatment time points.Results50 patients with DS-TB and 30 patients with MDR-TB were recruited in the German identification cohorts (DS-GIC and MDR-GIC, respectively); 28 patients with DS-TB and 32 patients with MDR-TB in the German validation cohorts (DS-GVC and MDR-GVC, respectively); and 52 patients with MDR-TB in the Romanian validation cohort (MDR-RVC). A 22-gene RNA model (TB22) that defined cure-associated end-of-therapy time points was derived from the DS- and MDR-GIC data. The TB22 model was superior to other published signatures to accurately predict clinical outcomes for patients in the DS-GVC (area under the curve 0.94, 95% CI 0.9–0.98) and suggests that cure may be achieved with shorter treatment durations for TB patients in the MDR-GIC (mean reduction 218.0 days, 34.2%; p<0.001), the MDR-GVC (mean reduction 211.0 days, 32.9%; p<0.001) and the MDR-RVC (mean reduction of 161.0 days, 23.4%; p=0.001).ConclusionBiomarker-guided management may substantially shorten the duration of therapy for many patients with MDR-TB.
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- Heyckendorf, J, et al.
(author)
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Treatment responses in multidrug-resistant tuberculosis in Germany
- 2018
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In: The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease. - : International Union Against Tuberculosis and Lung Disease. - 1815-7920. ; 22:4, s. 399-
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Journal article (peer-reviewed)
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- Jafari, C, et al.
(author)
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Rapid diagnosis of pulmonary tuberculosis by combined molecular and immunological methods
- 2018
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In: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 51:5
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Journal article (peer-reviewed)abstract
- Diagnosing pulmonary tuberculosis (TB) may be delayed until culture results become available.We ascertained the accuracy of a stepwise diagnostic algorithm for the rapid diagnosis of pulmonary TB by GeneXpert from sputum and/or bronchoalveolar lavage (BAL) followed by aMycobacterium tuberculosis-specific BAL ELISPOT assay in patients with a suspected diagnosis of pulmonary TB at a clinical referral centre in Germany.Among 166 patients with a presumptive diagnosis of pulmonary TB, 81 cases were confirmed byM. tuberculosisculture from sputum and/or BAL. In 66 out of 81 (81.5%) cases, patients initially hadM. tuberculosisdetected by GeneXpert from sputum; in addition, six out of 81 (7.4%) cases were diagnosed by GeneXpert on BAL fluid (together 72 out of 81 (88.9%) patients). Out of the remaining nine patients with negative GeneXpert results from sputum and BAL, BAL ELISPOT identified eight patients with culture-confirmed TB correctly (median time to culture positivity 26 days). At a cut-off of >4000 early secretory antigenic target-6- or culture filtrate protein-10-specific interferon-γ-producing lymphocytes per 1 000 0000 lymphocytes, the specificity of the BAL ELISPOT for active TB was 97%.In low TB incidence countries, nearly all patients with active pulmonary TB can be identified within the first few days of clinical presentation using a stepwise strategy with GeneXpert and BAL ELISPOT.
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- Kalsdorf, B, et al.
(author)
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[Tuberculosis]
- 2015
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In: Deutsche medizinische Wochenschrift (1946). - : Georg Thieme Verlag KG. - 1439-4413 .- 0012-0472. ; 140:20, s. 1508-1512
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Journal article (peer-reviewed)
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