Active Pulmonary Tuberculosis Group Research Articles

Evaluation of cytokine profiles related to Mycobacterium tuberculosis latent antigens using a whole-blood assay in the Philippines.

There is no useful method to discriminate between latent tuberculosis infection (LTBI) and active pulmonary tuberculosis (PTB). This study aimed to investigate the potential of cytokine profiles to discriminate between LTBI and active PTB using whole-blood stimulation with Mycobacterium tuberculosis (MTB) antigens, including latency-associated antigens. Patients with active PTB, household contacts of active PTB patients and community exposure subjects were recruited in Manila, the Philippines. Peripheral blood was collected from the participants and used for whole-blood stimulation (WBS) with either the early secretory antigenic target and the 10-kDa culture filtrate protein (ESAT-6/CFP-10), Rv3879c or latency-associated MTB antigens, including mycobacterial DNA-binding protein 1 (MDP-1), α-crystallin (Acr) and heparin-binding hemagglutinin (HBHA). Multiple cytokine concentrations were analyzed using the Bio-Plex™ multiplex cytokine assay. A total of 78 participants consisting of 15 active PTB patients, 48 household contacts and 15 community exposure subjects were eligible. The MDP-1-specific IFN-γ level in the active PTB group was significantly lower than that in the household contact group (p < 0.001) and the community exposure group (p < 0.001). The Acr-specific TNF-α and IL-10 levels in the active PTB group were significantly higher than those in the household contact (TNF-α; p = 0.001, IL-10; p = 0.001) and community exposure (TNF-α; p < 0.001, IL-10; p = 0.01) groups. However, there was no significant difference in the ESAT-6/CFP-10-specific IFN-γ levels among the groups. The patterns of cytokine profiles induced by latency-associated MTB antigens using WBS have the potential to discriminate between LTBI and active PTB. In particular, combinations of IFN-γ and MDP-1, TNF-α and Acr, and IL-10 and Acr are promising. This study provides the first demonstration of the utility of MDP-1-specific cytokine responses in WBS.

Significance of detecting the levels of miR-29a, survivin and interferon gamma release assay in patients with lung cancer and tuberculosis.

When lung cancer is combined with concurrent tuberculosis (TB), it increases the difficulty of diagnosis and treatment, leading to missed and/or misdiagnosed cases. To provide reference markers for the clinical diagnosis of patients with lung cancer complicated by active pulmonary TB (APT). The concentration of survivin in diseased tissue, and miR-29a and IGRAs interferon gamma (IFN-γ) in serum were evaluated in 25 patients with non-small cell lung carcinoma (NSCLC) complicated by APT, 32 patients with NSCLC and 30 patients with APT. The expression of miR-29a in serum of patients with APT was higher than in patients with NSCLC complicated by APT (least significant difference (LSD)-t = 4.724, p < 0.001), and the NSCLC group (LSD-t = 6.619, p < 0.001). Furthermore, patients with NSCLC complicated by APT had higher miR-29a concentration than the NSCLC group. The rate of positive survivin expression in NSCLC (χ2 = 23.418, p < 0.001) and NSCLC combined with APT group (χ2 = 17.160, p < 0.001) was significantly higher than in patients with APT. The concentration of IFN-γ in serum of the NSCLC complicated by APT group (LSD-t = 2.912, p = 0.004) and the APT group (LSD-t = 4.452, p < 0.001) was higher than in the NSCLC group. The level of IFN-γ in serum of the NSCLC complicated by APT group were higher than in the APT group, but there was no statistical difference. The levels of MiR-29a, Survivin and IFN-γ was helpful for differential diagnosis of lung cancer and tuberculosis.

IFN-gamma and IL-4 Secretion After Stimulation of EC610 Fusion Antigens (ESAT-6-CFP-10) in Patients With Active Pulmonary TB And Latent TB

Tuberculosis (TB) is an infectious disease caused by the bacterium Mycobacterium tuberculosis (M.tb) and is still a major health problem in the world. Immunity against tuberculosis is very complex because it involves almost all components of the immune system. One of the cells that are responsible for cell-mediated immunity are lymphocytes, especially T helper lymphocytes are divided into Th1 (proinflammatory cytokines IFN-?) and Th2 (anti-inflammatory cytokine IL-4). EC610 fusion antigens (ESAT-6-CFP-10) is a peptide containing a specific antigen M.tb. Order to determine the differences between the secretion of IFN-? and IL-4 after stimulation EC610 fusion antigens (ESAT-6-CFP-10) in patients with active pulmonary TB and latent TB.Research with a quasi-experimental design in laboratory in vitro in patients with active pulmonary tuberculosis group of 21 samples and 28 samples of latent TB. Venous blood sampling in vitro anticoagulants heparin and PBMCs isolated using a Ficoll-Paque ™, then cultured with antigen fusion EC610 for 24-72 hours with a CO2 incubator at a temperature of 370 C. The levels of IFN-? and IL-4 by ELISA method. Statistical analysis with alternative test non-parametric Mann Whitney.IFN-? secretion in patients with active pulmonary TB group (6700 pg / ml) was higher than the latent (6000 pg / ml) after stimulation by antigen fusion EC610, but not significant (p = 0.769). While the secretion of IL-4 levels (180 and 60 pg / ml) there was a significant difference between the groups (p = 0.000).

Clinical application value of γ-IFN release assay combined with CA-125 in diagnosis of active pulmonary tuberculosis

Objective: To evaluate the diagnosis of interferon gamma release assay (IGRA) combined with tumor marker carbohydrate antigen-125 (CA-125) in active pulmonary tuberculosis (PTB). Methods: One hundred and three patients with active PTB (48 definite and 55 clinical diagnosed), 646 patients with non-PTB pulmonary disease and 60 normal controls hospitalized in Beijing Tongren Hospital, Capital Medical University between January 2014 and December 2016 were retrospectively investigated. Blood samples were collected to determine the IGRA and CA-125 level by enzyme-linked immunosorbent assay and electrochemiluminescence, respectively. The CA-125 level of patients with active PTB, non-PTB pulmonary disease and normal controls were compared. Subsequently, the best cut-off value of CA-125 for diagnosing PTB was calculated based on 60 active PTB cases and 60 normal controls. Methodological evaluation of IGRA, CA-125 and combination of these two tests (both positive) for active PTB diagnosing were performed based on 43 active PTB cases and all the non-PTB pulmonary disease cases. Results: The median values of CA-125 among definite and clinical diagnosis groups of active PTB were 55.00 (25.35, 156.90) U/ml and 81.50 (39.40, 138.00) U/ml, respectively. There was no difference between the two groups (U=1 093.00, P>0.05). And the CA-125 level of male and female PTB patients were also undifferentiated (U=1 124.00, P>0.05). There were statistically significant differences in CA-125 levels between the active PTB group and all other non-PTB groups (all P<0.001), including those who had ever closely contacted with TB patients. The area under the ROC curve constructed by CA-125 for diagnosing active PTB was 0.933. And the best cut-off value of CA-125 was 22.00 U/ml. Based on this cut-off value, the accuracy, sensitivity and specificity of CA-125 for diagnosing active PTB were 70.5% (486/689), 86.0% (37/43) and 69.5% (449/646). The accuracy, sensitivity and specificity of IGRA for diagnosing active PTB were 73.3% (480/689), 90.7% (39/43) and 68.3%(441/64). The accuracy, sensitivity and specificity of IGRA combined with CA-125 for diagnosing active PTB were 90.6% (624/689), 76.7% (33/43), 91.5% (591/646). Both of the accuracy and the false positive ratio of this combinational method (8.5%, 55/646) were significantly lower than two indexes individually used (χ(2)=94.461, 88.261, P<0.001). However, the false negative ratio was increased to 23.3% (10/43) by combinational method. Conclusion: IGRA combined with CA-125 has a certain clinical value in diagnosis of active PTB, especially when the evidences of bacterial is not available.

Using cytometric bead arrays to detect cytokines in the serum of patients with different types of pulmonary tuberculosis.

Cytokines play a crucial role in mediating immune responses to tuberculosis (TB). The aim of this study was to evaluate the levels of cytokines in patients with different forms of pulmonary tuberculosis (PTB) and identify valuable cytokine biomarkers for the diagnosis of PTB. We measured the levels of six cytokines (interleukin (IL-2, IL-4, IL-6, and IL-10), tumor necrosis factor (TNF-α), and interferon-γ (IFN-γ)) in the serum of healthy donors (n = 30). Patients with active PTB (n = 46) and those with latent tuberculosis infection (LTBI, n = 38) were examined using cytometric bead arrays. The levels of the six cytokines in the serum samples were measured promptly, sensitively, and simultaneously. The levels of IL-2, IL-6, IL-10, and IFN-γ were significantly higher in the PTB group compared with those reported in the healthy donors (P < 0.01 or P < 0.05). In addition, significantly higher levels of IL-2, IL-6, IL-10, and IFN-γ were found in the active PTB group compared with those observed in the LTBI group (P < 0.01 or P < 0.05). However, the levels of IL-4 and TNF-α in the sera of patients from the PTB group did not show a significant correlation with those measured in the healthy donor group. Our data demonstrated that IL-2, IL-6, IL-10, and IFN-γ may be useful in the auxiliary diagnosis of tuberculosis and as biomarkers for distinguishing LTBI from TB.

INTERFERON GAMMA AND INTERLEUKIN-10 LEVELS IN PBMC OF ACTIVE AND LATENT TUBERCULOSIS PATIENTS AS WELL AS HEALTHY INDIVIDUALS

Tuberculosis (TB), an infectious disease caused by a Mycobacterium tuberculosis, is still a health problem in Indonesia, and the world. One of the failures to control the TB epidemic is due to the lack of effective vaccines available today. Protective immune responses to M.tuberculosis are dominated by cellular immunity and less by humoral immunity. IFN-γ, and IL-10 play a role in the protection of against M.tuberculosis, and the pathogenesis of TB. Fusion antigen ESAT-6-CFP-10 has a strong antigenicity to T cells and stimulates specific cellular immune responses, thereby providing benefit in immune responses that are protective against M.tuberculosis infection. The aimed of this study was to know the difference betwen IFN-γ, and IL-10 levels on PBMC culture of active TB, latent TB, and healthy people after ESAT-6-CFP-10 fusion antigen stimulation. This study used an in vitro of quasi experimental design in PBMC cultures of active TB, latent TB, and healthy people groups stimulated by ESAT-6-CFP-10 antigen fusion Mycobacterium tuberculosis. IFN-γ, and IL-10 levels were measured by ELISA method. The results were analyzed by one-way ANOVA. The mean levels of IFN-γ post-stimulation of ESAT-6-CFP-10 fusion antigens did not differ (p=0.359) in the active pulmonary TB group (0.07 - 2114), latent TB (6.84 - 1381) and healthy people 1.88 - 1807.70), as well as the mean levels of IL-10 (p=0.712) in the active pulmonary TB (16.70 - 328.80), latent TB (29.70 - 323.60 ) and healthy people (31.30 - 958). There were no significant differences in levels of IFN-γ and IL-10 in active TB, latent TB, and healthy people after stimulation by fusion antigen ESAT-6-CFP-10.

Presepsin as a novel diagnostic biomarker for differentiating active pulmonary tuberculosis from bacterial community acquired pneumonia

BackgroundThe expression of presepsin in active pulmonary tuberculosis (APTB) is unknown. We observed the expression of presepsin in APTB, and to evaluate the value for discriminating between APTB and bacterial community acquired pneumonia (BCAP). MethodsConsecutive APTB patients who were accurately diagnosed by sputum culture and BCAP patients were enrolled from August 2013 to July 2015. Clinical data were collected, and plasma presepsin concentrations were tested. Receiver operating characteristic (ROC) curves were performed for diagnostic analysis. ResultsIn all, 133 healthy individuals, 103 APTB and 202 BCAP patients were enrolled. Presepsin concentrations in APTB group (218.0 [146.0, 368.0] pg/ml) were higher than those in the healthy control group (128.0 [101.5, 176.5] pg/ml, P<0.001), and lower than the concentrations measured in the BCAP group (532.0 [364.0, 852.3] pg/ml, P<0.001). Simple APTB and miliary tuberculosis patients showed no significant differences in presepsin concentrations. Compared with both Gram-positive and negative bacteria, Mycobacterium tuberculosis caused a limited increase of presepsin. With the cut-off value set at 401pg/ml, presepsin demonstrated high positive predictive value, allowing initial discriminating between APTB and BCAP. Presepsin combined with CURB-65 score could significantly improve the discrimination ability. ConclusionsPresepsin concentrations in APTB patients were slightly increased, and may be helpful for initial discrimination between APTB and BCAP.

Mean platelet volume as an inflammation marker in active pulmonary tuberculosis

Background: The mean platelet volume (MPV) reflects the size of platelets. It has been shown to be inversely correlated with level of the inflammation in some chronic inflammatory diseases. This prospective study aims to show the usability of MPV as an inflammation marker in patients with active pulmonary tuberculosis (PTB) by comparison with healthy controls. In addition, its relationships with other inflammatory markers such as C-reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) as well as with the radiological extent of disease were examined.&#x0D; Methods: This study included 82 patients with active PTB and 95 healthy subjects (control group). Whole blood counts, CRP level, and ESR were compared between the two groups. In the PTB group, the relationships between the radiological extent of disease and the MPV and other inflammation markers were investigated.&#x0D; Results: The MPV was 7.74 ± 1.33/μL in the PTB group and 8.20 ± 1.13/μL in the control group (p = 0.005). The blood platelet count, CRP level, and ESR were significantly higher in the active PTB group than in the control group (p &lt; 0.0001). In the PTB group, CRP levels (r = 0.26, p = 0.003) and ESR (r = 0.39, p = 0.003), but not MPV (p = 0.80), were significantly correlated with the radiologic extent of the disease.&#x0D; Conclusions: The MPV was lower in patients with PTB than in healthy controls, however, the difference was limited. The MPV does not reflect the severity of the disease. The use of MPV as an inflammation marker and a negative acute-phase reactant in PTB does not seem to be reliable.

Mean platelet volume as an inflammation marker in active pulmonary tuberculosis

BackgroundThe mean platelet volume (MPV) reflects the size of platelets. It has been shown to be inversely correlated with level of the inflammation in some chronic inflammatory diseases. This prospective study aims to show the usability of MPV as an inflammation marker in patients with active pulmonary tuberculosis (PTB) by comparison with healthy controls. In addition, its relationships with other inflammatory markers such as C-reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) as well as with the radiological extent of disease were examined.MethodsThis study included 82 patients with active PTB and 95 healthy subjects (control group). Whole blood counts, CRP level, and ESR were compared between the two groups. In the PTB group, the relationships between the radiological extent of disease and the MPV and other inflammation markers were investigated.ResultsThe MPV was 7.74 ± 1.33/μL in the PTB group and 8.20 ± 1.13/μL in the control group (p = 0.005). The blood platelet count, CRP level, and ESR were significantly higher in the active PTB group than in the control group (p < 0.0001). In the PTB group, CRP levels (r = 0.26, p = 0.003) and ESR (r = 0.39, p = 0.003), but not MPV (p = 0.80), were significantly correlated with the radiologic extent of the disease.ConclusionsThe MPV was lower in patients with PTB than in healthy controls, however, the difference was limited. The MPV does not reflect the severity of the disease. The use of MPV as an inflammation marker and a negative acute-phase reactant in PTB does not seem to be reliable.

MCP-1 −2518 A/G functional polymorphism is associated with increased susceptibility to active pulmonary tuberculosis in Tunisian patients

Monocyte chemoattractant protein-1 (MCP-1) plays crucial role in protective immunity against Mycobacterium tuberculosis (MT). In this study, we examined whether single nucleotide polymorphism (SNP) -2518 A/G (rs 1024611) of MCP-1 affect the susceptibility to active tuberculosis (TB) in Tunisian populations. Genomic DNA from patients with active TB (168 cases of pulmonary TB and 55 cases of extrapulmonary TB) and ethnically controls (150 cases) was genotyped for the MCP-1 -2518 A/G SNP by polymerase chain reaction fragment length polymorphism (PCR-RFLP). We observed that -2518 G allele and GG genotype (high MCP-1 producer) frequencies were significantly more elevated in active pulmonary TB group in comparison to control group [34 vs. 22%; P = 0.0007; 15 vs. 5%, P corrected for the number of genotypes (Pc) = 0.015; respectively]. Additionally, they were associated with increased risk development of this clinical form of TB [odds ratio (OR) = 1.83, 95% confidence intervals (CI) = 1.26-2.66; OR = 3.1, 95% CI = 1.28-7.76; respectively]. However, wild type allele -2518 A and AA genotype were over-represented in control group (78 and 62%) and seem to be protective factors against TB. Moreover, -2518 AA genotype was more frequent in control group and was associated with resistance against development of active pulmonary TB (OR = 0.56, 95% CI = 0.35-0.89, Pc = 0.03). Our findings confirm the key role of -2518 A/G SNP of MCP-1 and support its association with resistance/susceptibility to the development of active pulmonary TB in the Tunisian population.

High-resolution CT for identify patients with smear-positive, active pulmonary tuberculosis

PurposeThis study evaluates the use of high-resolution computed tomography (HRCT) to differentiate smear-positive, active pulmonary tuberculosis (PTB) from other pulmonary infections in the emergency room (ER) setting.MethodsOne hundred and eighty-three patients diagnosed with pulmonary infections in an ER were divided into an acid fast bacillus (AFB) smear-positive, active PTB group (G1 = 84) and a non-AFB smear-positive, pulmonary infection group (G2 = 99). HRCT images from a 64-Multidetector CT were analyzed, retrospectively, for the morphology, number, and segmental distribution of pulmonary lesions.ResultsUtilizing multivariate analysis, five variables were found to be independent risk factors predictive of G1: (1) consolidation involving the apex segment of right upper lobe, posterior segment of the right upper lobe, or apico-posterior segment of the left upper lobe; (2) consolidation involving the superior segment of the right or left lower lobe; (3) presence of a cavitary lesion; (4) presence of clusters of nodules; (5) absence of centrilobular nodules. A G1 prediction score was generated based on these 5 criteria to help differentiate G1 from G2. The area under the receiver operating characteristic (ROC) curve was 0.96 ± 0.012 in our prediction model. With an ideal cut-off point score of 3, the specificity, sensitivity, positive predictive value (PPV), and negative predictive value (NPV) are 90.9%, 96.4%, 90.0% and 96.8%, respectively.ConclusionThe use of this AFB smear-positive, active PTB prediction model based on 5 key HRCT findings may help ER physicians determine whether or not isolation is required while awaiting serial sputum smear results in high risk patients.