Li L.,Soochow University of China |
Li L.,Key Laboratory on Technology for Parasitic Disease Prevention and Control |
Guo Z.,Soochow University of China |
Wang J.,Wuxi Infectious Diseases Hospital |
And 3 more authors.
Digestive Diseases and Sciences | Year: 2012
Background: Alpha-fetoprotein detection is currently mainly used in clinic for diagnosis of primary hepatocellular carcinoma (HCC). However, its sensitivity and specificity are not satisfying. Approximately 60-80 % of patients with HCC have an established background of chronic infection with hepatitis B virus (HBV). Aims: To investigate the potential of serum microRNAs (miRNAs) as biomarkers for HBV-related HCC. Methods: This study was divided into two phases: firstly, marker (miR-95, miR-18a, miR-10b, miR125a, and miR-378) detection by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) in sera from HBV patients with HCC (n = 15) and health subject (n = 15); and, secondly, marker validation by real-time qRT-PCR on HBV patients with HCC (n = 86) or hepatitis or cirrhosis (n = 30), and healthy subject (n = 45). Results: Serum miR-18a was significantly higher in HBV patients with HCC than healthy controls (p<0.01); serum miR-378 was significantly lower in HBV patients with HCC compared to healthy control (p<0.05). Receiver operating characteristic (ROC) curve analyses suggested that serum miR-18a had significant diagnostic value for HBV-related HCC. MiR-18a yielded an area under the curve (AUC) of ROC of 0.881 with 86.1 % sensitivity and 75.0 % specificity in discriminating HBV-related HCC from healthy controls, and an AUC of ROC of 0.775 with 77.2 % sensitivity and 70.0 % specificity in discriminating HBV-related HCC from chronic hepatitis or cirrhosis. Conclusions: Our results suggest that serum miR-18a might serve as a novel and potential noninvasive biomarker for HBV-related HCC screening. © Springer Science+Business Media, LLC 2012.
Shen L.,Shanghai Pulmonary Hospital |
Shi H.,Shanghai Pulmonary Hospital |
Gao Y.,Fudan University |
Ou Q.,Wuxi Infectious Diseases Hospital |
And 6 more authors.
Tuberculosis | Year: 2016
PD-1 is a cell surface receptor of activated T and B lymphocytes and it's role in tuberculosis is controversial because of lack of congruence between clinical study and animal model. To investigate the immunological pathogenesis mechanisms of tuberculosis and to develop the immune therapy target essential for controlling tuberculosis, here we explored the expression characteristics and dynamic changes of PD-1/PD-L1 pathway in different CD4+T cell subsets. We enrolled 24 human subjects including 15 active tuberculosis (ATB) patients and 9 healthy donors (HD). The expressions of PD-1 and PD-L1 on CD4+T cells increased significantly in ATB patients than HD. ATB patients had a higher proportion of regulatory T cells (Treg, CD4+CD25 + Foxp3+) than HD. The expressions of PD-1 and PD-L1 increased remarkably on CD4+T cell subsets, including Treg cells, Tresp (CD4+CD25−) cells and Teff (CD4+CD25 + Foxp3-) cells. Finally, clinical improvement following effective anti-TB therapy is correlated with significantly decreased expression of PD-1 in Tresp and Teff cells, but not in Treg cells. Thus, expression profiles of PD-1 in T cell subpopulations may be used as a candidate to predict the clinical efficacy of anti-tuberculosis therapy. Modulation of PD-1/PD-L1 pathway in CD4 subsets may offer an immunotherapy target for the control of tuberculosis. © 2016 Elsevier Ltd
Zhang B.,Wuxi Infectious Diseases Hospital |
Hu M.,Wuxi Infectious Diseases Hospital |
Zhang P.,Nanjing Medical University |
Cao H.,Wuxi Infectious Diseases Hospital |
And 3 more authors.
Brazilian Journal of Medical and Biological Research | Year: 2013
Primary biliary cirrhosis (PBC) is a chronic and slowly progressive cholestatic liver disease of autoimmune etiology. A number of questions regarding its etiology are unclear. CD4+CD25+regulatory T cells (Tregs) play a critical role in self-tolerance and, for unknown reasons, their relative number is reduced in PBC patients. B-cell-activating factor (BAFF) is a key survival factor during B-cell maturation and its concentration is increased in peripheral blood of PBC patients. It has been reported that activated B cells inhibit Treg cell proliferation and there are no BAFF receptors on Tregs. Therefore, we speculated that excessive BAFF may result in Treg reduction via B cells. To prove our hypothesis, we isolated Tregs and B cells from PBC and healthy donors. BAFF and IgM concentrations were then analyzed by ELISA and CD40, CD80, CD86, IL-10, and TGF-b expression in B cells and Tregs were measured by flow cytometry. BAFF up-regulated CD40, CD80, CD86, and IgM expression in B cells. However, BAFF had no direct effect on Treg cell apoptosis and cytokine secretion. Nonetheless, we observed that BAFF-activated B cells could induce Treg cell apoptosis and reduce IL-10 and TGF-b expression. We also showed that BAFF-activated CD4+T cells had no effect on Treg apoptosis. Furthermore, we verified that bezafibrate, a hypolipidemic drug, can inhibit BAFF-induced Treg cell apoptosis. In conclusion, BAFF promotes Treg cell apoptosis and inhibits cytokine production by activating B cells in PBC patients. The results of this study suggest that inhibition of BAFF activation is a strategy for PBC treatment.
PubMed | Fudan University, Shanghai Pulmonary Hospital, Tongji University and Wuxi Infectious Diseases Hospital
Type: | Journal: Tuberculosis (Edinburgh, Scotland) | Year: 2016
PD-1 is a cell surface receptor of activated T and B lymphocytes and its role in tuberculosis is controversial because of lack of congruence between clinical study and animal model. To investigate the immunological pathogenesis mechanisms of tuberculosis and to develop the immune therapy target essential for controlling tuberculosis, here we explored the expression characteristics and dynamic changes of PD-1/PD-L1 pathway in different CD4+T cell subsets. We enrolled 24 human subjects including 15 active tuberculosis (ATB) patients and 9 healthy donors (HD). The expressions of PD-1 and PD-L1 on CD4+T cells increased significantly in ATB patients than HD. ATB patients had a higher proportion of regulatory T cells (Treg, CD4
PubMed | Fudan University and Wuxi Infectious Diseases Hospital
Type: | Journal: Scientific reports | Year: 2016
The aim of this study was to explore the diagnostic value of IL-31 levels in the pleural fluid and plasma to differentially diagnose tuberculous and malignant pleural effusion. We enrolled 91 cases, including tuberculous pleural effusion (TPE, n=50), malignant pleural effusion (MPE, n=41), other cases including pneumonia with pleural fluid, pulmonary tuberculosis and healthy people as controls. Whole blood was stimulated with the M. tuberculosis-specific antigens and plasma was collected. The multiplex bead-based cytokine immunoassay was employed to measure the levels of various cytokines. IL-31 was found to be the most prominent cytokine (P<0.0001), and with an optimal cut-off value of 67.5pg/mL, the sensitivity and specificity for the diagnosis of TPE were 86% and 100%, respectively. Furthermore, the tuberculosis-specific IL-31 levels in the plasma of TPE patients were higher than that of MPE patients (P=0.0002). At an optimal cut-off value of 23.9pg/mL, the sensitivity and specificity for the diagnosis of TPE were 92.9% and 85.7%, respectively. Ultimately, the combination of pleural fluid with the plasma tuberculosis-specific IL-31 levels improved the sensitivity and specificity to 94.0% and 95.1%, respectively. Thus, we identified a novel biomarker for the diagnosis of TPE for clinical application.
PubMed | Fudan University, Tongji University and Wuxi Infectious Diseases Hospital
Type: | Journal: Scientific reports | Year: 2016
The role of the PD-1/PD-L pathway in a murine model of tuberculosis remains controversial regarding viral infections and clinical tuberculosis. We conducted a case-control study to investigate the modulating role and mechanism of the PD-1/PD-L pathway in patients with active tuberculosis. Fifty-nine participants, including 43 active tuberculosis (ATB) patients and 16 healthy controls (HC), were enrolled. Cell surface staining and flow cytometry were used to detect the expressions of PD-1 and its ligands on T cells and monocytes. Intracellular cytokine staining was used to determine the PPD-specific IFN--secreting T-cell proportion. CD4