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Objective:To investigate the influence and potential mechanism of mannose-capped lipoarabinomannan (ManLAM) to B cells responding to Mycobacterium tuberculosis (Mtb) infection. Methods:B cells were separated from patients with active pulmonary tuberculosis using magnetic beads and then stimulated with ManLAM in combination with CE protein. Flow cytometry was performed to evaluate the apoptosis, proliferation and activation of B cells. The secretion of cytokines and CE protein-specific IgG subclasses were detected by ELISA. ELISPOT assay was used to analyze the influence on the differentiation of B cells into CE protein-specific antibody-secreting cells (ASCs).Results:ManLAM inhibited the CE protein-induced proliferation and activation of B cells and the production of pro-inflammatory cytokines, resulting in significantly increased secretion of the immunosuppressive cytokine IL-10. It also inhibited the differentiation of B cells into CE protein-specific IgG secretory cells, but had no significant influence on the differentiation to IgM secretory cells. Moreover, ManLAM inhibited the secretion of CE protein-specific IgG1 and IgG3 and induced the secretion of immunosuppressive IgG4 via TLR2.Conclusions:This study suggested that ManLAM could inhibit the anti-tuberculosis immune response of B cells, which provided new theoretical reference for better understanding the immune escape mechanism in Mtb infection.
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Objective To explore the relationship between 24 h ambulatory blood pressure monitoring (24h-ABPM) parameters, circadian rhythm and urinary albumin to creatinine ratio (UACR), urineβ2 microglobulin (β2-MG) in elderly patients with hypertension. Methods One hundred and forty-eight patients with essential hypertension (≥60 years old) were included in this study. 24h-ABPM was performed, and nocturnal blood pressure decline rate (BPR) was calculated. The patients were divided into two groups according the BPR:dipper group with 40 cases and non-dipper group with 108 cases. The levels of 24h-ABPM parameters, UACR and β2-MG were compared between two groups, and the relationship between UACR and 24h-ABPM parameters were analyzed. Results The levels of 24hSBP, dSBP and 24hDBP in two groups had no significant differences (P>0.05). Compared with those in dipper group, the levels of nSBP, nDBP in non-dipper group were significantly increased, and the level of dDBP was significantly decreased, P0.05). The result of Sspearman analysis showed that UACR had significant correlation with 24hDBP, nDBP, 24hSBP, nSBP and 24hPP (P<0.05 or<0.01). The result of multivariate linear regression analysis showed that UACR was independently correlated with nSBP (P<0.05). Conclusions The abnormal circadian rhythm in elderly hypertensive patients is closely related to early renal damage.
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Objective Pleural effusion of patients with tuberculous pleurisy was analyzed by ultra high performance liquid chromatography-mass spectrometry (UPLC-MS).Orthogonal partial least squares discriminant analysis (OPLS-DA) model was established for searching and analyzing the potential metabolic biomarkers to provide new ideas for the early diagnosis of tuberculosis pleurisy.Methods Totally 166 cases of pleural samples were collected from November 2012 to September 2013 in Tianjin Haihe Hospital (tuberculosis pleurisy 83 cases,bacterial pleurisy 31 cases,lung cancer 30 cases and heart failure 22 cases)and metabonomics quantitative analysis was conducted.Quantitative analysis of metabolic methods was enrolled.Orthogonal partial least squares discriminant analysis (OPLS-DA) model was constructed by the pattern recognition method.Based on the OPLS-DA model,potential biomarkers was filtered preliminary by variable importance in the projection (VIP) and VIP confidence interval value.The specific metabolites were determined by applying non-parametric test(Kruskal-Wallis H test)by using SPSS 17.0,and potential metabolic biomarkers were screened.Results The prediction accuracy of OPLS-DA model was 100％ (38/38),which illustrated that the model could verify the tuberculous pleurisy group and the control group accurately.Based on the data of metabolites,46 potential metabolites were finally screened and 5 metabolites were identified with statistically significant differences (P ＜ 0.05).The data of tuberculosis pleurisy group showed a significant increase in 17a,20a-Dihydroxy cholesteryl,phospholipid [20∶4 (8Z,11Z,14z,17Z)] (1 188 670.00),tocotrienols (1 051 760.00) and phospholipid(O-18:0) (434 394.00) compared with the lung cancer group(735 615.00,336 815.00,324 563.00,193 055.00),bacterial pleurisy group (1 678 805.00,598 256.50,699 384.00,343 866.00),and heart failure group(535 842.00,253 503.00,234 503.00,130 185.00) (H =26.787,18.680,26.193,21.024,P ＜0.01),and a significant decrease in L-phenylalanine(245 976.00)compared with the lung cancer group(753 033.50),bacterial pleurisy group (357 278.00),and heart failure group(586 678.00) (H =13.635,P ＜ 0.01).Conclusions The OPLSDA model constructed on the basic of UPLC-MS technology platform can verify the tuberculous pleurisy group and the control group accurately,and the study provides new ideas and methods for identifying features of tuberculous pleurisy markers and early diagnosis.
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Objective To establish a diagnostic model of multiple cytokines for differential diagnosis of tuberculous pleural effusion , and compare its diagnostic accuracy with tuberculosis infected T cells detection ( T-SPOT.TB ) in order to evaluate its diagnostic performance.Methods Case-control study.Totally 147 patients with pleural fluid in Tianjin Haihe Hospital were enrolled and categorized as tuberculous pleural effusion group ( n=95 ) and malignant pleural effusion group ( n=52 ) from December 2011 to June 2013.Pleural effusion cytokines including interferon-γ( IFN-γ) , C-X-C motif chemokine 10 (CXCL-10), tumor necrosis factor-α(TNF-α), vascular endothelial growth factor (VEGF), IL-2, IL-16, IL-17, IL-27 and IL-33 were tested by liquid chip technology and analyzed by Binary Logistic regression and receiver operating characteristic curve (ROC), and the pleural effusion was also detected by tuberculosis infected T cells detection ( T-SPOT.TB) as a control.Results The comparison of the AUC of cytokines is:CXCL-10>IL-27>IFN-γ>IL-33 >IL-17>IL-16>TNF-α>VEGF>IL-2; After that, CXCL-10, IFN-γ, IL-27 and IL-33 were included the Binary Logistic regression model.The regression equation is P=1/1+e-( -16.851+0.390 ×IFN-γ+0.006 ×IL-27+0.020 ×IL-33).The AUC, sensitivity and specificity of the diagnostic model were 99.5%, 96.84%, and 98.08%, respectively.Both AUC and sensitivity of the diagnostic model were superior to those of any single index.Compared with T-SPOT.TB (0.995 ±0.003), the AUC of the diagnostic model (0.921 ±0.023) was significantly greater ( Z=3.235, P 0.05).The Kappa of the two methods was 0.795, which meant fine agreement of the evaluations of the two raters.Conclusion The application of liquid array technology of high sensitivity and repeatability with high throughput provided a novel insight and method in the clinical diagnosis , treatment and prevention for tuberculous pleural effusion scientifically and accurately.
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Objective To explore the diagnostic value of combined detection of the liquid array technology, interfer-on (IFN)-γand IFN-γ-inducible protein (IP)-10 in the rapid, accurate diagnosis and differential diagnosis of tuberculous pleural effusions. Methods Patients with transudative pleural effusions were divided into tuberculous pleural effusion group (n=52) and malignant pleural effusion group (n=38). The method of T-SPOT.TB was used to detect the number of effec-tor T cells sensitized to Mycobacterium tuberculosis and spot forming cells (SFCs). The liquid array technology was used to detect the level of IFN-γand IP-10. Logistic regression was used to analyze and compare the diagnostic value of the two-method combination. Results The diagnostic sensitivity, specificity and the area under the ROC curve (AUC) of T-SPOT. TB were 90.38%, 84.21%, and 0.938 (95%CI:0.867-0.978), respectively. The diagnostic sensitivity, specificity and AUC of combined detection of IFN-γand IP-10 were 98.08%, 97.37%, and 0.995 (95%CI:0.951-1.000), respectively. There was no significant difference in the diagnostic sensitivity and specificity between the two methods, and the diagnostic agreement for the two diagnostic methods was fine (Kappa=0.703). The difference of AUC between the methods was significantly differ-ent (Z=1.996, P<0.05). The method of combined detection of IFN-γand IP-10 showed the larger AUC (AUC=0.995). Con-clusion The combined diagnosis meets the clinical needs of rapid, accurate diagnosis and differential diagnosis for tuber-culous pleural effusion by simultaneously assaying the level of IFN-γand IP-10 using the liquid array technology.