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Method for detecting active tuberculosis

An active tuberculosis and non-tuberculosis technology, applied in biochemical equipment and methods, microbial determination/inspection, measuring devices, etc.

Inactive Publication Date: 2018-12-21
UCL BUSINESS PLC
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  • Abstract
  • Description
  • Claims
  • Application Information

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  • Method for detecting active tuberculosis
  • Method for detecting active tuberculosis
  • Method for detecting active tuberculosis

Examples

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Embodiment 1

[0408] Example 1: Comparison of the blood transcriptome in active TB and after prolonged recovery

[0409] The AdjuVIT study population included HIV-negative patients with positive smears and cultures for pulmonary TB, in which, by comparison with recovered subjects drawn from the same cohort, two to four years after completion of TB treatment, The present invention seeks to identify the peripheral blood transcriptional signature of active TB in the above patients (Table 1). The analysis revealed statistically significant and >2-fold gene expression differences among 204 unique protein-coding transcripts ( figure 1 A). Consistent with other published data, active TB in this cohort was associated with increased expression of genes involved in the immune response ( figure 1 B). To assess the generality of this transcriptional signature in other patient cohorts with active TB, compared to healthy volunteers (Berry et al., 2010) or subjects with LTBI (Bloom et al., 2012) , the...

Embodiment 2

[0413] Example 2: Support Vector Machine Classification of Active TB by Comparison with Health Status

[0414] In order to distinguish individual cases by their blood transcriptome, the present invention uses SVM to obtain a discriminative model from the training data and classify the subsequent test cases. Using 51 transcripts differentially expressed in active TB compared to other healthy states in multiple cohorts ( figure 1 C), The present invention uses the AdjuVIT research dataset to train an SVM to distinguish active TB cases from recovered cases. The inventors then evaluated the performance of this SVM model in classifying samples from three independently published studies of HIV-negative subjects, including a total of 325 cases. These include the two studies mentioned above, including data from active TB and healthy volunteers (Berry cohort) (Berry et al., 2010) or active TB and latent TB (Bloom cohort) (Bloom et al., 2012) , and additional data from a multicenter A...

Embodiment 3

[0416] Example 3: BATF2 distinguishes active TB from healthy status in multiple study cohorts

[0417] Having identified peripheral blood BATF2 transcript levels in the AdjuVIT cohort as a biomarker of active TB, the present inventors sought to test its performance in multiple independent cohorts. Regardless of HIV status, BATF2 expression was significantly higher in patients with active TB than in healthy volunteers (Berry cohort) (Berry et al., 2010) and patients with LTBI (Bloom and Kaforou cohorts) (Bloom et al. , 2012; Kafourou et al., 2013) of BATF2 expression, representing data from a total of 402 patients ( image 3 A). In HIV-negative patients in these studies, peripheral blood BATF2 expression that differentiated active TB cases from various healthy cases was described with a ROCAUC score of 0.93 to 0.99 in each cohort ( image 3 B). In HIV-infected patients (ROC AUC of 0.84) in the Kaforou cohort, BATF2 levels were not well able to distinguish active TB cases fro...

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Abstract

The present invention relates to a method of determining the presence or absence of active tuberculosis in a sample, in particular, comprising determining the levels of one or more biomarkers selectedfrom basic leucine zipper transcription factor ATF-like 2 (BATF2), cluster of differentiation 177 (CD177), haptoglobin (HP), immunoglobulin J chain (IGJ) and galectin 10 (CLC), in said sample. Uses of biomarkers of the invention and kits for performing the method of the invention are also described.

Description

technical field [0001] The present invention relates to the diagnosis of tuberculosis. In particular, the invention relates to methods of determining the presence or absence of active tuberculosis in a subject by analyzing a sample from the subject for one or more biomarkers. Background technique [0002] Each year, 10.5 million cases of active tuberculosis (TB) cause >1.5 million deaths. Only about 60% of patients receive a laboratory diagnosis of active TB. This depends on the microbial identification of Mycobacterium tuberculosis (Mtb), which is often marred by the need to obtain inaccessible samples from the site of disease and by the poor susceptibility of samples to extrapulmonary TB (Boehme et al. 2013; Norbis et al., 2014; Denkinger et al., 2014; WHO Global tuberculosis report, 2015). The fastest liquid culture systems can detect bacteria within 10 to 19 days and require six weeks for a definitive negative result, delaying clinical decision-making (Dinnes et al...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/689
CPCC12Q1/6883C12Q2600/112C12Q2600/158C12Q1/689A61P31/06G01N33/6893G01N2800/12G01N2800/26G01N2800/56
Inventor 马达德·努萨德格珍妮弗·罗阿德里安·马蒂诺
Owner UCL BUSINESS PLC
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