Marker For Active Tuberculosis Research Articles

Diagnostic value of FCGR1B gene transcription level in active tuberculosis

Objective: To investigate the diagnostic potential of Fc fragment of IgG receptor 1b gene (FCGR1B) transcription level in active tuberculosis. Methods: From February to September of 2018, we collected peripheral blood from patients with active tuberculosis, latent tuberculosis infection (LTBI), cured patients with tuberculosis, healthy people and patients with pneumonia in the Eighth Medical Center of PLA General Hospital. Peripheral blood mononuclear cells (PBMCs) were isolated for total RNA extraction and cDNA synthesis. The expression of FCGR1B mRNA in PBMCs was detected by quantitative real-time PCR (QPCR). Nonparametric test was used to compare the differential expression of FCGR1B mRNA between patients with active tuberculosis and control groups, and the relationships between FCGR1B mRNA expression and patient's illness condition and inflammatory indexes were analyzed by Correlation analysis. The potential of FCGR1B mRNA as a diagnostic marker for active tuberculosis was evaluated by receiver operating characteristic curve (ROC) analysis. Results: The expression of FCGR1B mRNA in PBMCs from patients with active tuberculosis was significantly increased when compared with non-tuberculosis controls, including individuals with LTBI, healthy people, cured patients with tuberculosis and patients with pneumonia (u=2 081, P<0.001). The expression of FCGR1B mRNA was higher in patients with tuberculosis who had more bacteria(H=12.35, P=0.015), and was correlated with the C-reactive protein (CRP) (r=0.30, P=0.008). ROC analysis showed that FCGR1B mRNA could distinguish active tuberculosis from non-tuberculosis with area under curve (AUC) of 0.849. The sensitivity and specificity were 71.43% and 84.17% respectively. The AUC of FCGR1B mRNA in distinguishing extra-pulmonary tuberculosis from controls was 0.906. The sensitivity and specificity were 84.62% and 91.89%, respectively. Conclusion: FCGR1B mRNA is a potential molecular marker for diagnosis of active tuberculosis.

A Novel Urine Method for the Diagnosis of Active Tuberculosis by Immunoassay for the Detection of ESAT-6 Using Hydrogel Nanoparticles in HIV Patients

Background: In patients with HIV, conventional tests are of low sensitivity; therefore, a new diagnostic test with hydrogel nanoparticles with reactive blue dye is proposed, which allows the capture, conservation and concentration of ESAT-6 in urine. NIPAs are copolymers that capture low molecular weight proteins and protect against enzymatic degradation. Using an immunoassay, it is possible to detect and quantify ESAT-6 present in urine as a possible marker of active TB. Design/Methods: Study in Lima, Peru, HIV+ participants, ≥18 years with and without tuberculosis (TB). Smear microscopy, culture in solid medium and urine immunoassay were performed. The reference was the diagnosis of TB by radiological or clinical microbiological criteria (indication for TB treatment). There were 2 preanalytical processes: untreated and treated urine (centrifuged, heated), then incubation with NIPAm. After washing, elution, sonication, heat and centrifugation, the final eluate was obtained. This was placed on nitrocellulose membranes, which by means of fixation and incubation processes with anti-ESAT-6 and anti-IgG antibodies, revelation with C-DiGit&reg Blot Scanner and FluorChem R FR0001. Calibration curves were included in the membranes, density was measured using Image J software. ROC curves, sensitivity and specificity were obtained. Results: The result by groups was HIV+ patient: ROC: 0.75, cut-off point ≥24.06 ng/ml, sensitivity 76.32%, specificity 68.89%, patients ≤200 cells CD4 mm3/ml, ROC: 0.78, cutoff point ≥26.20 ng/ml, sensitivity 75.86%, specificity 71.88%, patients >200 CD4 mm3 cells/ml, ROC: 0.73, cutoff point ≥24.6 CD4 mm3/ml, sensitivity 73.68%, specificity 73.68%. Conclusions: The ESAT-6 detection assay using NIPAm was effective, with higher rates in patients with ≤200 CD4 cells/mm3, the test being more sensitive than smear and culture, but less specific.

An Inflammatory Story: Antibodies in Tuberculosis Comorbidities.

Mycobacterium tuberculosis (Mtb) resides in a quarter of the world's population and is the causative agent for tuberculosis (TB), the most common infectious reason of death in humans today. Although cellular immunity has been firmly established in the control of Mtb, there is growing evidence that antibodies may also modulate the infection. More specifically, certain antibody features are associated with inflammation and are divergent in different states of human infection and disease. Importantly, TB impacts not just the healthy but also those with chronic conditions. While HIV represents the quintessential comorbid condition for TB, recent epidemiological evidence shows that additional chronic conditions such as diabetes and kidney disease are rising. In fact, the prevalence of diabetes as a comorbid TB condition is now higher than that of HIV. These chronic diseases are themselves independently associated with pro-inflammatory immune states that encompass antibody profiles. This review discusses isotypes, subclasses, post-translational modifications and Fc-mediated functions of antibodies in TB infection and in the comorbid chronic conditions of HIV, diabetes, and kidney diseases. We propose that inflammatory antibody profiles, which are a marker of active TB, may be an important biomarker for detection of TB disease progression within comorbid individuals. We highlight the need for future studies to determine which inflammatory antibody profiles are the consequences of comorbidities and which may potentially contribute to TB reactivation.

Significant Increase in Natural-Killer T Cells in Patients with Tuberculosis Complicated by Type 2 Diabetes Mellitus

This study examined the frequency of Vα24(+)/Vβ11(+) natural-killer T (NKT) cells from peripheral blood and bronchoalveolar lavage fluid in pulmonary tuberculosis (TB) patients with or without diabetes mellitus (DM). The clinical grade of TB was significantly higher among diabetic patients. NKT cells from both peripheral blood and bronchoalveolar lavage were significantly increased in diabetic TB patients compared with non-diabetic TB patients. This may be due to the generally higher bacillary burden in diabetic TB patients. NKT cells from peripheral blood mononuclear cells in TB patients with or without DM were significantly increased, compared with levels in non-TB diabetic patients and healthy controls. The measurement of NKT cells from peripheral blood has the potential to be a reliable, non-invasive, practical diagnostic marker for active TB.

Use of Antibodies in Lymphocyte Secretions for Detection of Subclinical Tuberculosis Infection in Asymptomatic Contacts

We have previously demonstrated that Mycobacterium bovis BCG-specific immunoglobulin G antibodies in lymphocyte secretions (ALS) can be employed as a marker for active tuberculosis (TB). We aimed to determine whether the ALS method allows detection of subclinical TB infection in asymptomatic individuals. A prospective study of family contacts (FCs) of patients with active TB and healthy controls was performed. Thirteen of 42 FCs had high ALS responses, including 6 FCs who subsequently developed active TB. No correlation was observed between the tuberculin skin test and the ALS responses in the FCs (r = 0.1, P = 0.23). Among patients with active TB, BCG-specific ALS responses steadily declined from the time of diagnosis through 6 months following antimycobacterial chemotherapy (P = 0.001). The ALS assay enabled detection of infection in exposed symptom-free contacts, who are at greater risk for developing active TB. The method may also allow discrimination between effective treatment of active infection and suboptimal response to therapy.