Active Tuberculosis Group Research Articles

CT Imaging Characteristics of Nontuberculous Mycobacteria Lung Disease, Active Tuberculosis and Multi-Drug Resistant Tuberculosis.

The differential diagnosis of nontuberculous mycobacteria (NTM) lung disease, active tuberculosis (ATB) and multi-drug resistant tuberculosis (MDR-TB) remains difficult. To explore the CT imaging characteristics of NTM lung disease, ATB and MDR-TB for differential diagnosis. Patients with NTM lung disease (n=200), ATB (n=200) and MDR-TB (n=200) who were examined and treated from August 2013 to May 2021 were included. Their chest CT imaging results were retrospectively analyzed, and the imaging characteristics were compared. The proportion of cases complicated with underlying lung disease, cough and hemoptysis was significantly higher in NTM group than those in ATB and MDR-TB groups (P<0.05). Compared with ATB and MDR-TB groups, NTM group had significantly more cases of nodule-bronchus dilation type, but significantly fewer cases of nodule-mass type and other types (P<0.05). In NTM group, the cases of thin-wall cavity, bronchiectasis and centrilobular nodules increased, but the detection rate of thick-wall cavity, lung consolidation, atelectasis, lung damage, lung volume reduction, intrapulmonary calcification, hilar and mediastinal lymph node calcification, acinar nodules, pleural thickening and pleural effusion declined compared with ATB and MDR-TB groups (P<0.05). The detection rates of lesions, cavities and bronchiectasis in the lingual lobe of left lung and middle lobe of right lung were significantly higher in NTM group than those in ATB and MDR-TB groups (P<0.05). The imaging characteristics of NTM lung disease are quite similar to those of ATB and MDR-TB, but they can be differentially diagnosed through the types of cavities and nodules, incidence rate of bronchiectasis, and differences in lung consolidation, lung damage, calcification, pleural thickening and pleural effusion.

1406. Hepatitis B and C Prevalence in Patients with Active and Latent Tuberculosis in an Ethnically Diverse Area of London, UK

BackgroundNorth West London has one of the highest tuberculosis (TB) rates in the UK, at 24.8 per 10,000. The UK prevalence of hepatitis B virus (HBV) is 0.1-0.5% and for hepatitis C virus (HCV) is 0.5-1%. Chronic infection with HBV or HCV can lead to an increased risk of adverse treatment outcomes, such as drug-induced liver injury (DILI) in patients with active or latent TB. National guidelines recommend routinely screening for HBV/HCV prior to initiating TB treatment. Our objectives were to 1) evaluate the HBV/HCV screening practice in local TB clinics, 2) establish the prevalence of HBV/HCV in patients receiving TB treatment.MethodsRetrospective analysis of laboratory and medical records of patients treated for active or latent TB identified from the London TB register and clinic records from 01/01/2018 to 31/12/2020 from London North West NHS Trust.Results1409 patients received treatment for TB during the time period of interest; 574 (40.7%) had active disease and 835 (59.3%) had latent infection. 966/1409 patients (68.56%) were screened for HBV and HCV. 55.9% of the active TB group and 77.2% of the latent infection group were tested. 66 (6.8%) patients had isolated anti-HBc positivity, 22 (2.3%) were HBV surface antigen positive and 8 (0.8%) were HCV-antibody positive. HBV surface antigens were more prevalent in active TB patients: 9/321 (2.80%) with active TB versus 13/645 (2.02%) with latent TB. 36/321 (11.21%) active TB patients had HBV core antibodies compared to 30/645 (4.65%) latent TB patients (p < 0.001). Three patients started antiviral treatment following their viral hepatitis diagnosis (one with HBV, two with HCV).ConclusionThe prevalence of chronic HBV in the study population was higher than the estimated UK prevalence. Fifteen diagnoses of hepatitis were new, allowing specialist referral for monitoring of fibrosis and development of hepatocellular carcinoma. Three patients required hepatitis treatment. 6.8% of patients were positive for anti-HBc and therefore identified as being at future risk of HBV reactivation if requiring immunosuppressive therapies.TB disproportionately affects marginalised communities; screening for viral hepatitis in TB clinic represents an opportunity to target these hard-to-reach groups to maximise the impact of public health interventions.Disclosures All Authors: No reported disclosures

ILC2s induce adaptive Th2-type immunity in different stages of tuberculosis through the Notch-GATA3 pathway

The study is to investigate the roles of group 2 innate lymphoid cells (ILC2s) in different courses of tuberculosis (TB). Serum and PBMCs were respectively isolated from the TST negative, LTBI (latent TB infection), ATB (active TB) and RTB (recurrent TB) patients. Flow cytometry was used to detect Th1, Th2 and ILC2s in the peripheral blood. The mRNA and protein levels of GATA3, RORα, CRTH2, Hes1, Notch1, NF-κB, and ID2 were detected by qRT-PCR and Western blotting. ILC2 cells from ATB and RTB patients were stimulated with rJagged2 or DAPT in vitro, and co-cultured with CD4+ T cells from TST negative group. ELISA was used to detect cytokine levels. The results showed that compared with the TST negative or LTBI group, Th2 cells and serum IL-4 in ATB group increased dramatically, accompanied by an increase of Th2/Th1 ratio in ATB patients, especially in RTB group. However, ILC2s in the ATB and RTB group increased significantly, along with increased GATA3, RORα, and CRTH2 levels. After rJagged2 stimulation in vitro, the levels of Hes1, Notch1, NF-κB, RORα, GATA3 and ID2 and those of IL-4, IL-5 and IL-13 were significantly increased. These effects were abrogated by DAPT treatment. Then, ILC2s, especially those from RTB patients, induced Th2-type immune response after co-culturing with CD4+ T cells. In conclusion, our results suggest that ILC2s may promote Th2-type immune response in different stages of TB via the Notch-GATA3 pathway.

COMBINATION OF T-SPOT.TB RATIO AND EXPRESSION OF CD161 ON T LYMPHOCYTES IN DISCRIMINATING ACTIVE TB AND LATENT TB INFECTION

TOPIC: Chest Infections TYPE: Original Investigations PURPOSE: Interferon-gamma releasing assay using qualitative T-SPOT.TB cannot discriminate active tuberculosis (ATB) from latent tuberculosis infection (LTBI). Previous research suggests that interleukin-17 secreting from CD161-expressing T-lymphocytes is low in patients developing ATB. This study aims to investigate the performance of quantitative T-SPOT.TB alone and in combination with CD161-expressing T-lymphocytes in differentiating ATB from LTBI. METHODS: This cross-sectional study was conducted in a university hospital between January 2020 and December 2020. Enrolled subjects were categorized as the following: (i) newly microbiologically confirmed pulmonary TB (ATB), (ii) close-contacts with normal chest radiograph and positive qualitative T-SPOT.TB (LTBI), and (iii) negative T-SPOT.TB (control). All subjects underwent quantitative measurement for the ratio of TB-specific antigen spots over positive control-PHA spots (TBAg/PHA), and flow cytometry for CD161-expressing T-lymphocytes (index-CD161 calculated using the lymphocyte to monocyte ratio multiplied by the percentage of CD161+ expression on CD8+ T-lymphocyte). The group comparisons were made and the cutoff values for TBAg/PHA ratio alone and combined with index-CD161 were determined for the sensitivity, specificity, and area under the receiver operating characteristics curve (AUROC). RESULTS: A total of 113 subjects were enrolled (36 active TB, 18 LTBI, and 59 control). The TBAg/PHA ratio was significantly higher in the ATB group than in the LTBI and control groups (p<0.001). The index-CD161 was significantly lower in the ATB group than in the LTBI and control groups (p<0.001). Using the TBAg/PHA ratio value of ≥ 0.039, the sensitivity, specificity and AUROC were 72%, 72% and 0.76, respectively. When the index-CD161 value of ≤ 145 was analyzed with the TBAg/PHA ratio in logistic regression model, the diagnostic performance of ATB was improved by increasing the sensitivity, specificity and AUROC to 88%, 93% and 0.95, respectively. CONCLUSIONS: Combination of TBAg/PHA ratio in the T-SPOT.TB test with CD161 expressing T-lymphocytes helps to discriminate active TB from LTBI. CLINICAL IMPLICATIONS: Sequential addition of CD161-T cell expression response to TBAg/PHA ratio increases performance to distinguish ATB from LTBI and aids clinician to thoroughly investigate for ATB in clinically suspected of tuberculosis. DISCLOSURES: No relevant relationships by Putthapoom Lumjiaktase, source=Web Response No relevant relationships by DR MEKAVUTHIKUL, source=Web Response No relevant relationships by Prapaporn Pornsuriyasak, source=Web Response

The Significance of Differences in Melanocortin 3 Levels and their Relationship with Pulmonary Tuberculosis and Body Mass Index

BACKGROUND: Melanocortin 3 Receptors (MC3R) levels plays a role in many biological systems, including energy homeostasis and regulation of fat metabolism. However, very few have researched the relationship between MC3R and tuberculosis (TB) and body mass index. AIM: This study explores the differences in serum MC3R levels in active TB, household contacts, and control groups, as well as at different body mass index status. This study tries to find out the relationship between MC3R and other variables. METHODS AND MATERIALS: Blood samples were taken from 53 active TB patients, 49 household contacts, and 30 healthy people as controls. The 132 samples were subjected to IGRA and ELISA examinations to determine differences in MC3R levels in all groups. RESULTS: The highest mean of MC3R levels were found in the active TB group at 1.259.55 (p = 0.028) and had a positive correlation with a value of p = 0.008. In the sex group, men had the highest levels (p = 0.551). In the 30–49 year age group, the median value increased significantly in the three groups (p = 0.028), and there was a correlation between MC3R and the 17–29 year age group, although the correlation was negative (p = 0.021), in the 30–49 year age group with a positive correlation (p = 0.050). The mean MC3R value increased significantly in the overweight group in the three groups (p = 0.006) but did not significantly correlate. CONCLUSION: The high level of MC3R in TB patients is related to its role as a defence against microbes that enter the body through the immune process to prevent further infection and inflammation. Meanwhile, high levels of MC3R in excess Body mass index were associated with the function of MC3R as an inhibitor of pro-opiomelanocortin (POMC) neurons to release α-MSH.

Comparison of QuantiFERON-TB Gold Plus and QuantiFERON-TB Gold In-Tube tests for patients with active and latent tuberculosis: A prospective cohort study

IntroductionWe aimed to determine the diagnostic performance and clinical value of the QuantiFERON-TB Gold In-Tube (QFT-GIT) and QuantiFERON-TB Gold Plus (QFT-Plus) tests in patients with active tuberculosis (TB) or latent TB infection (LTBI). MethodsWe prospectively enrolled 140 patients, including 63 with active TB and 77 with LTBI, between March 2017 and October 2018. QFT-GIT and QFT-Plus were performed simultaneously in all subjects. ResultsQFT-Plus and QFT-GIT test results showed significant agreement, in both active TB and LTBI patients, in terms of the interferon-γ concentration and interpretation result. QFT-Plus had higher sensitivity than QFT-GIT for predicting active TB (82.5% vs. 77.8%) and showed fewer false-negative and indeterminate results in both active TB and LTBI patients due to its “TB2 tube”. The QFT-Plus TB2-TB1 value was higher in the active TB group than in the LTBI group. The QFT-Plus TB1-Nil and TB2-Nil values were useful in predicting remote LTBI, rather than recent LTBI. ConclusionsQFT-Plus showed good agreement with QFT-GIT in both active TB and LTBI patients, and higher sensitivity for predicting active TB than QFT-GIT. The QFT-Plus TB2 tube results, which reflect CD8+ T cell immunity, may improve predictive accuracy and detection of the immune response associated with active TB and LTBI.

Cell population data in identifying active tuberculosis and community-acquired pneumonia.

ObjectiveLeukocyte morphological parameters known as CPD (cell population data) is detected by hematology analyzer UniCel DxH800 with VCS technology. This study aimed to investigate the diagnostic efficacy of morphological changes in CPD parameters in distinguishing active tuberculosis from community-acquired pneumonia.MethodsFrom October 2018 to February 2019, 88 patients with active tuberculosis, 78 patients with community-acquired pneumonia, and 89 healthy controls were enrolled in this study. CPD was obtained using Unicel DxH800 analyzer for all whole blood samples, one-way ANOVA (non-parametric) and area analysis under ROC curve were performed.ResultsThe neutrophil mean conductivity (NMC), monocyte mean volume (MMV), monocyte mean conductivity (MMC), lymphocyte percentage (LY%), and monocyte percentage (MO%) were significantly higher in the active tuberculosis group than in the community-acquired pneumonia group. The white blood cell (WBC) count and neutrophil percentage (NE%) were significantly lower in the active tuberculosis group than in the community-acquired pneumonia group. The analysis of the area under the ROC curve proved that WBC count, neutrophil percentage (NE%), lymphocyte percentage (LY%), and monocyte percentage (MO%) did not achieve a higher area under the curve (AUC: 0.63, 0.71, 0.62, and 0.7, respectively). However, the AUC of NMC, MMV, and MMC in the CPD parameters was 0.951, 0.877, 0.98, respectively, and the simultaneous measurement of the three parameters was 0.99. The sensitivity and specificity were 98.5% and 91.1%, respectively.ConclusionThe combined diagnosis of NMC, MMV, and MMC could assist the clinical diagnosis of active tuberculosis and community-acquired pneumonia.

First clinical evaluation of the QIAreachTM QuantiFERON-TB for tuberculosis infection and active pulmonary disease

Objective1) to compare the QIAreachTM QuantiFERON-TB (QIAreach QFT) vs. QuantiFERON®-TB Gold Plus assay (QFT-Plus) to detect tuberculosis (TB) infection; 2) to evaluate diagnostic sensitivity of QIAreach QFT using active TB as surrogate for TB infection; 3) to preliminarily evaluate QIAreach QFT in immunocompromised individuals. MethodsQIAreach QFT measures the level of interferon-γ (IFN-γ) in plasma specimens from blood stimulated by ESAT-6 and CFP-10 peptides in one blood collection tube (equivalent to the TB2 tube of the QFT-Plus). QIAreach QFT was applied to plasma samples from 41 patients with pulmonary TB and from 42 healthy or low-TB-risk individuals. ResultsSensitivity and specificity of QIAreach QFT vs. QFT-Plus were 100% (41/41) and 97.6% (41/42), respectively; overall concordance was 98.8% (82/83). All samples were measured within 20 min. The time to result of each sample was significantly correlated with IFN-γ level with a natural logarithmic scale (r = -0.913, p < 0.001). Seven cases in the active TB group were immunocompromised (CD4 <200/μL) and tested positive by QIAreach QFT. ConclusionsQIAreach QFT provides an objective readout with a minimum blood sample volume (1 mL/subject), potentially being a useful point-of-care screening test for TB infection in high-TB-burden, low-resource countries and for immunocompromised patients.

Combined analysis of whole blood interferon gamma release assay and complete blood count analysis for rapid discrimination of active tuberculosis and latent tuberculosis infection

Tuberculosis (TB), which is caused by Mycobacterium tuberculosis (MTB), is a serious infectious disease with high infection and mortality rates and is a public health problem around the world. According to the World Health Organization (WHO) report, one-third of the world's population is latently infected with MTB, and 5 to 10% of those with latent TB infection (LTBI) have the potential to develop active TB once in their lifetime. Therefore, TB management for promptly distinguishing LTBI from active TB and for proper treatment is important. LTBI is currently diagnosed using the tuberculin skin test (TST) and interferon gamma (IFN-γ) release assay (IGRA). However, this test is substantially limited by its inability to distinguish active TB from LTBI. It is necessary to discover indicators that can be used for effective TB management and to develop diagnostic methods. In the present study, we used IGRA and complete blood count (CBC) analysis for discrimination of active TB, LTBI, and healthy control groups. The results showed that the number of WBC was significantly increased in the group with active TB (p < 0.0100) and level of hemoglobin (Hb) was significantly decreased (p < 0.0010) in the CBC than those of the healthy control and LTBI groups. In the WBC differential count, the number of neutrophils and monocytes were increased (p < 0.0010) in active TB group, where as those of lymphocytes were significantly decreased (p < 0.0100) in active TB group compared healthy control group. Results verified that the levels of total WBC, Hb, neutrophils, lymphocytes and monocytes were statistically significant (p < 0.0500) and the AUC was approximately 0.8613. In addition, receiver operating characteristic (ROC) curve analysis was performed to confirm the clinical usefulness between active TB and healthy control groups. In conclusion, based on these data demonstrated that the usefulness of these potential indicators for differential diagnosis, according to the result can be provided for effective diagnosis and treatment by comparing the expression patterns of the markers in the whole blood of the active TB, LTBI, and healthy control groups. Furthermore, this study needs to investigate a larger number of clinical specimens later to develop biomarkers according to the state of infection with MTB such as LTBI and active TB, as well as after treatment.

The TBAg/PHA ratio in T-SPOT.TB assay has high prospective value in the diagnosis of active tuberculosis: a multicenter study in China

BackgroundThe positive rate of pathogenic examination about tuberculosis is low. It is still difficult to achieve early diagnosis for some TB patients. The value of Interferon-gamma release assays (IGRA) in the diagnosis of active tuberculosis remains controversial. The purpose of this multicenter prospective study was to verify and validate the role of TBAg/PHA ratio (TB-specific antigen to phytohaemagglutinin) of T-SPOT.TB assay in diagnosing ATB.MethodsWe prospectively enrolled 2390 suspected pulmonary tuberculosis patients with positive T-SPOT assay results from three tertiary hospitals.ResultsA total of 1549 ATB (active tuberculosis) patients (including 1091 confirmed and 458 probable ATB) and 724 non-tuberculosis (non-TB) patients with positive T-SPOT results were included. The results of this study showed that ESAT-6 and CFP-10 in the T-SPOT.TB assay were significantly higher in the ATB group compared with the non-TB group, while PHA was lower in the ATB group. Results of ESAT-6, CFP-10 and PHA show a certain diagnostic performance, but moderate sensitivity and specificity. The TBAg/PHA ratio, a further calculation of ESAT-6, CFP-10 and PHA in T-SPOT.TB assay showed improved performance in the diagnosis of active Tuberculosis. If using the threshold value of 0.2004, the specificity and sensitivity of TBAg/PHA ratio in distinguishing ATB from non-TB were 92.3% and 74.4%, PPV was 95.4, PLR was 9.6.ConclusionBy recalculating the results of T-SPOT.TB Assay, the TBAg/PHA ratio shows high prospect value in the diagnosis of active tuberculosis in high prediction areas.

Overview of Tuberculosis among Children of Madurese Ethnicity in East Java, Indonesia

ABSTRACT This study aimed to find the characteristics of tuberculosis (TB) in children among the Madurese ethnicity in Indonesia. A descriptive study with a cross-sectional approach was used. The study used Indonesian TB scoring on 23 Madurese children consisting of 16 children with active TB and 7 healthy control children. Data was analysed with SPSS software and Pearson’s test. The findings showed that children who contacted adults with TB active associated with the incident of active TB (OR=64 (3.83-2623.17)). A positive result of the tuberculin test was experienced in active TB participants (OR=136 (5.58-20266.2)). While weight or nutritional status has a good category (OR=0.31 (0.03-3.07) and children with TB active indicated the symptom of cough more than 3 weeks (OR=7 (0.60-185.21)). Those who had swollen lymph nodes were in an active TB group (OR=128 (5.22-19130.8)), as well as had a chest X-ray suggestive of TB (OR= 0.02 (0-0.26)).

IL-1RA in the supernatant of QuantiFERON-TB Gold In-Tube and QuantiFERON-TB Gold Plus is useful for discriminating active tuberculosis from latent infection

IntroductionThe new-generation QuantiFERON (QFT)-TB Gold Plus (QFT-Plus) is expected to be useful because it includes a new peptide that is supposed to induce a CD8+ T cell response. There is a need for a new marker with sensitivity higher than that of the conventional IFN-γ release assays owing to false-negative results in the latter. This study aimed to compare cytokines in QFT-plus and QuantiFERON-Gold In-Tube (QFT-GIT) supernatants to discriminate between active tuberculosis and latent tuberculosis infection (LTBI). MethodsA cross-sectional study was conducted at Tokyo National Hospital, wherein 21 LTBI patients and age and sex-matched active TB patients were randomly selected. The levels of various cytokines were measured and compared using the MAGPIX System, and receiver operating characteristic (ROC) curves were generated. ResultsIL-1RA, IFN-γ, CXCL10/IP-10, and CCL4/MIP-1β levels were higher in the active TB group than in the LTBI group in QFT-GIT antigen (GIT Ag) tubes. In QFT-plus tubes, IL-1RA was higher in TB1 and TB2 tubes, while CCL2/MCP-1 was higher only in TB2 tubes. In Nil tubes, CCL5/RANTES, TNF-α, PDGF-BB, and IL-2 levels were significantly higher in the active TB group. IL-1RA in GIT Ag tubes showed the highest area under the curve of 0.8367. The sensitivity and specificity of IL-1RA were 66.7% (95% confidence interval [CI]: 43.0–85.4) and 90.5% (95% CI: 69.6–98.8), respectively, which were the highest among the cytokines. ConclusionsIL-1RA level in the QFT-GIT supernatant can be a good marker for discriminating active TB from LTBI.

MicroRNA-23a-3p Down-Regulation in Active Pulmonary Tuberculosis Patients with High Bacterial Burden Inhibits Mononuclear Cell Function and Phagocytosis through TLR4/TNF-α/TGF-β1/IL-10 Signaling via Targeting IRF1/SP1.

The aim of this study is to explore the role of microRNAs (miR)-21/23a/146a/150/155 targeting the toll-like receptor pathway in active tuberculosis (TB) disease and latent TB infection (LTBI). Gene expression levels of the five miRs and predicted target genes were assessed in peripheral blood mononuclear cells from 46 patients with active pulmonary TB, 15 subjects with LTBI, and 17 non-infected healthy subjects (NIHS). THP-1 cell lines were transfected with miR-23a-3p mimics under stimuli with Mycobacterium TB-specific antigens. Both miR-155-5p and miR-150-5p gene expressions were decreased in the active TB group versus the NIHS group. Both miR-23a-3p and miR-146a-5p gene expressions were decreased in active TB patients with high bacterial burden versus those with low bacterial burden or control group (LTBI + NIHS). TLR2, TLR4, and interleukin (IL)10 gene expressions were all increased in active TB versus NIHS group. MiR-23a-3p mimic transfection reversed ESAT6-induced reduction of reactive oxygen species generation, and augmented ESAT6-induced late apoptosis and phagocytosis, in association with down-regulations of the predicted target genes, including tumor necrosis factor (TNF)-α, TLR4, TLR2, IL6, IL10, Notch1, IL6R, BCL2, TGF-β1, SP1, and IRF1. In conclusion, the down-regulation of miR-23a-3p in active TB patients with high bacterial burden inhibited mononuclear cell function and phagocytosis through TLR4/TNF-α/TGF-β1/IL-10 signaling via targeting IRF1/SP1.

Differential expression of CD64 in patients with Mycobacterium tuberculosis infection: A potential biomarker for clinical diagnosis and prognosis.

To evaluate the clinical utility of neutrophil (n)CD64 index to diagnose pulmonary tuberculosis (PTB) and extrapulmonary TB (ePTB) and to predict the outcome of Mycobacterium tuberculosis infection. We recruited 189 patients with active TB and 140 controls and measured the differential expression of nCD64 index using flow cytometry. The receiver operating characteristics (ROC) curve analysis was performed to estimate the diagnostic performance of the nCD64 index and T‐SPOT.TB assay for the diagnosis of TB. Furthermore, we analysed whether the nCD64 index in patients with TB was correlated with inflammatory indicators. Finally, we assessed the prognosis of patients by following the dynamic changes of the nCD64 index once a week. The nCD64 index was significantly higher in active TB group (PTB and ePTB), than in the anti‐TB and healthy controls (HC) groups. The sensitivity and specificity of nCD64 index for the differential diagnosis of PTB and pneumonia (PN) patients were 68.33% and 77.55%, respectively. The sensitivity and specificity of nCD64 index for the diagnosis of tuberculous meningitis (TBM) were 53.85% and 100%, respectively. Furthermore, there was a weak correlation between the nCD64 index and inflammatory indicators. More importantly, with the improvement in patient condition, the nCD64 index started to decline in the first week of anti‐TB therapy and significantly decreased at 4 weeks after treatment. Our study demonstrated that the CD64 assay is a rapid, non‐invasive and stable method for clinical application, and the nCD64 index can serve as a potential biomarker for the diagnosis and prognosis of TB.

Association between type I interferon receptor 1 single nucleotide polymorphisms and susceptibility to tuberculosis

Objective To investigate the relationship between single nucleotide polymorphism (SNP) of type I interferon receptor 1 (IFNAR1) and susceptibility to tuberculosis in the Han population in southern China. Methods A case-control study was used, with 1 533 patients with active tuberculosis (including 1 432 tuberculosis and 101 extrapulmonary tuberculosis) as the case group, and 1 445 healthy people as the control group. Interferon (IFN) gene rs72552343, rs2834191, rs1012334, rs17875752, rs2843710, rs1041868 genotypes were detected by MassARRAY time-of flight mass spectrometry. The differences in the frequency of SNP alleles between the two groups were analyzed, and the differences in the frequency of rs72552343 TCC / Del locus in patients with pulmonary tuberculosis and extrapulgative tuberculosis were further compared. Results MassARRAY time-of-flight mass spectrometry can effectively detect the genotypes of six SNP loci. Among the 6 SNP loci, it was found that only the rs72552343 TCC/Del locus allele frequency was significantly different between the active tuberculosis group and the control group, and the rs72552343 TCC/Del locus TCC allele frequency was significantly increased ( OR =0.46; 95% CI =0.31 -0.70; P =0.000 2), the frequency of the other five SNP alleles was not significantly different between the two groups. In addition, the frequency of TCC alleles at rs72552343 TCC / Del loci in patients with extrapulmonary tuberculosis was not significantly different from that in patients with tuberculosis ( OR =0.88; 95% CI =0.20-3.74; P =0.86). Conclusion The IFN gene rs72552343 TCC / Del site SNP is related to susceptibility to tuberculosis. The TCC allele is a susceptibility gene for tuberculosis, but individuals carrying the TCC allele have the same risk of active pulmonary tuberculosis as those with extrapulmonary tuberculosis. 摘要：目的 探究Ⅰ型干扰素受体 1 (typeⅠinterferon receptor 1, IFNAR1) 单核苷酸多态性 (single nucleotide poly⁃ morphism, SNP) 与结核病易感性的关系。 方法 应用病例-对照研究方法, 以深圳市第三人民医院 1 533 例活动性结核 病患者 (包括 1 432 例肺结核、101 例肺外结核) 作为病例组, 1 445 例健康人群作为对照组。运用 MassARRAY 飞行时间 质 谱 技 术 , 通 过 检 测 Ⅰ 型 干 扰 素 (interferon, IFN) 基 因 rs72552343、rs2834191、rs1012334、rs17875752、rs2843710、rs1041868 位点基因型, 分析两组间 SNP 等位基因频率差异, 同时进一步比较肺结核与肺外结核病患者 rs72552343 TCC/Del 位点等位基因频率差异。 结果 用 MassARRAY 飞行时间质谱技术可以有效地检测 6 个 SNP 位点基因型。在 6 个 SNP 位点中, 发现仅 rs72552343 TCC/Del 位点等位基因频率在活动性结核组和对照组中差异有统计学意义 ( P 0.05)。另外, 发现肺外结核病患者 rs72552343 TCC/Del 位点 TCC 等位基因的频率与肺结核病患者差异无统计学意 义 ( OR =0.88; 95% CI =0.20~3.74; P =0.86)。 结论 IFN 基因 rs72552343 TCC/Del 位点 SNP 与结核易感性相关, 其 TCC 等位基因为结核易感基因, 但携带 TCC 等位基因的个体患活 动性肺结核与肺外结核的风险一致。

Profiling the mRNA and miRNA in Peripheral Blood Mononuclear Cells in Subjects with Active Tuberculosis.

PurposeTo identify candidate hub genes and miRNAs associated with active tuberculosis (ATB) and reveal the potential molecular mechanisms of disease progression.Patients and MethodsThe expression of mRNA and miRNA was evaluated in peripheral blood mononuclear cells (PBMC) from 4 ATB patients and 4 healthy donors (HD) using high throughput sequencing (HTS) and bioinformatics analysis. Moreover, differentially expressed miRNAs were validated with 35 ATB patients and 35 HDs using reverse transcription quantitative real-time PCR (RT-qPCR).ResultsA total of 2658 significantly differentially expressed genes (DEG) including 1415 up-regulated genes and 1243 down-regulated genes were identified in the ATB group compared with HDs, and the DEGs enriched in immune-related pathways, especially in TNF signaling pathway, cytokine–cytokine receptor interaction, mitogen-activated protein kinase (MAPK) signaling pathways and tuberculosis. Additionally, 10 hub genes were acquired according to protein–protein interaction (PPI) analysis of DEGs. Moreover, 26 differentially expressed miRNAs were found in ATB group compared with HDs. Furthermore, RT-qPCR results showed that hsa-miR-23a-5p (P=0.0106), hsa-miR-183-5p (P=0.0027), hsa-miR-193a-5p (P=0.0021) and hsa-miR-941(P=0.0001) were significantly increased in the ATB patients compared with HD group, and the hsa-miR-16-1-3p was significantly decreased (P=0.0032).ConclusionOur research provided a characteristic profile of mRNAs and miRNAs expressed in ATB subjects, and 10 hub genes related with ATB were found, which will contribute to explore the role of miRNAs and hub genes in the pathogenesis of ATB, and improve the ability of differential diagnosis and treatment for the disease.

Blood M2a monocyte polarization and increased formyl peptide receptor 1 expression are associated with progression from latent tuberculosis infection to active pulmonary tuberculosis disease

ObjectivesThis study aims to explore the role of M2a polarization and formyl peptide receptor (FPR) regulation in the reactivation of Mycobacterium tuberculosis (Mtb) infection. MethodsM1/M2a monocyte percentage and FPR1/2/3 protein expression of blood immune cells were measured in 38 patients with sputum culture (+) active pulmonary TB disease, 18 subjects with latent TB infection (LTBI), and 28 noninfected healthy subjects (NIHS) using flow cytometry method. ResultsM1 percentage was decreased in active TB versus either NIHS or LTBI group, while M2a percentage and M2a/M1 percentage ratio were increased. FPR1 expression on M1/M2a, FPR2 expression on M1, and FPR3 expression of M1 were all decreased in active TB versus LTBI group, while FPR1 over FPR2 expression ratio on NK T cell was increased in active TB versus either NIHS or LTBI group. In 11 patients with active TB disease, M1 percentage became normal again after anti-TB treatment. In vitro Mtb-specific antigen stimulation of monocytic THP-1 cells resulted in M2a polarization in association with increased FPR2 expression on M2a. ConclusionsIncreased M2a and decreased M1 phenotypes of blood monocyte may serve as a marker for active TB disease, while decreased FPR1 on blood monocyte may indicate LTBI status.

Efficacy and safety of concurrent anti-tuberculosis treatment and chemotherapy in lung cancer patients with co-existent tuberculosis.

BackgroundThis retrospective study evaluated the safety and efficacy of concurrent anti-tuberculosis (TB) and chemotherapy treatment in patients with advanced lung cancer and active TB.MethodsWe retrospectively analyzed patients who were first diagnosed with advanced lung cancer and received first-line chemotherapy in Guangzhou Chest Hospital from 2015 to 2017. Patients were categorized into two groups (2:1): lung cancer patients without active TB (Group A), and lung cancer patients with active TB (Group B). Primary endpoints included adverse events (AEs), objective response rate (ORR), time to treatment failure, and overall survival (OS).ResultsA total of 99 patients were eligible (Group A, n=66; Group B, n=33). Grade ≥3 treatment-related AEs, primarily hematologic toxicity, occurred in 39.4% and 51.5% of patients in Groups A and B, respectively. The hypohepatia in both groups was generally at grade 1 or 2, with similar incidences (26% and 27%, respectively). After two cycles of chemotherapy, the ORR was 42.4% and 33.3% in Group A and B, respectively (P=0.383). The median time to treatment failure (TTF) was 7.0 and 5.6 months for Groups A and B, respectively (P=0.175). The median OS was 17.0 and 14.0 months for Groups A and B, respectively (P=0.312). After 3 months of anti-TB treatment, all patients achieved sputum acid-fast bacilli (AFB) smear conversion and absorption on imaging, and the end of follow-up observed no recurrence.ConclusionsConcurrent anti-TB and chemotherapy treatment did not increase hematological toxicity or hypohepatia in lung cancer patients with pulmonary TB.

Comparison of 68Ga-DOTANOC with 18F-FDG using PET/MRI imaging in patients with pulmonary tuberculosis

We compared the somatostatin analog radioligand, DOTANOC, with FDG, to determine whether there was increased detection of active or sub-clinical lesions in pulmonary tuberculosis (TB) with DOTANOC. Three groups were recruited: (1) active pulmonary TB; (2) IGRA-positive household TB contacts; (3) pneumonia (non-TB). DOTANOC PET/MRI followed by FDG PET/MRI was performed in active TB and pneumonia groups. TB contacts underwent FDG PET/MRI, then DOTANOC PET/MRI if abnormalities were detected. Quantitative and qualitative analyses were performed for total lung and individual lesions. Eight active TB participants, three TB contacts and three pneumonia patients had paired PET/MRI scans. In the active TB group, median SUVmax[FDG] for parenchymal lesions was 7.69 (range 3.00–15.88); median SUVmax[DOTANOC] was 2.59 (1.48–6.40). Regions of tracer uptake were fairly similar for both radioligands, albeit more diffusely distributed in the FDG scans. In TB contacts, two PET/MRIs had parenchymal lesions detected with FDG (SUVmax 5.50 and 1.82), with corresponding DOTANOC uptake < 1. FDG and DOTANOC uptake was similar in pneumonia patients (SUVmax[FDG] 4.17–6.18; SUVmax[DOTANOC] 2.92–4.78). DOTANOC can detect pulmonary TB lesions, but FDG is more sensitive for both active and sub-clinical lesions. FDG remains the preferred ligand for clinical studies, although DOTANOC may provide additional value for pathogenesis studies.

Comparison of QuantiFERON-TB Gold Plus, QuantiFERON-TB Gold In-Tube, and T-SPOT.TB among patients with tuberculosis

ObjectivesThis study evaluated the efficacy of the following interferon (IFN)-γ release assays (IGRAs): QuantiFERON-TB Gold Plus (QFT-Plus), QFT-Gold In-Tube (QFT-GIT), and T-SPOT. TB (T-SPOT) with the quantitative values of IFN-γ response. MethodsBlood samples were collected from patients with active tuberculosis (TB), latent TB infection (LTBI), individuals with previous TB infection, and healthy volunteers enrolled between May 2017 and June 2018. ResultsIGRAs results were analyzed in 175 subjects (76 had active TB, 14 had LTBI, 35 had prior TB infection, and 50 were healthy). QFT-Plus and QFT-GIT revealed equal efficacy for IFN-γ values, and the IFN-γ response in QFTs tended to increase with the spot counts in T-SPOT, with similar high sensitivities (approximately 90%) in the active TB group. The test concordance of two of three IGRAs was optimal among all subjects (κ coefficients: 0.82–0.96). Additionally, the median quantitative values of IFN-γ with QFT-Plus and QFT-GIT were higher in the active TB group than in the LTBI and previous TB groups. ConclusionThree IGRAs showed equivalent efficacy with high sensitivities and higher IFN-γ response in active TB group than that in non-active TB group.