BACKGROUND： Chronic hepatitis C virus （HCV） infection causes the skewing and activation of B cell subsets, but the characteristics of IgG＋ B cells in patients with chronic hepa- titis C （CHC） infection have not ...BACKGROUND： Chronic hepatitis C virus （HCV） infection causes the skewing and activation of B cell subsets, but the characteristics of IgG＋ B cells in patients with chronic hepa- titis C （CHC） infection have not been thoroughly elucidated. CD4＋CXCR5＋ follicular helper T （Tfh） cells, via interleukin （IL）-21 secretion, activate B cells. However, the role of CD4＋CXCR5＋ T cells in the activation ofIgG＋ B cells in CHC patients is not clear. METHODS： The frequency of IgG＋ B cells, including CD27-IgG＋ B and CD27＋IgG＋ B cells, the expression of the activation markers （CD86 and CD95） in IgG＋ B cells, and the percentage of circu- lating CD4＋CXCR5＋ T cells were detected by flow cytometry in CHC patients （n=70） and healthy controls （n=25）. The con- centrations of serum IL-21 were analyzed using ELISA. The role of CD4＋CXCR5＋ T cells in the activation of IgG＋ B cells was investigated using a co-culture system. RESULTS： A significantly lower proportion of CD27＋IgG＋ B cells with increased expression of CD86 and CD95 was observed in CHC patients. The expression of CD95 was negatively correlated with the percentage of CD27＋IgG＋ B cells, and it contributed to CD27＋IgG＋ B cell apoptosis. Circulating CD4＋CXCR5＋ T cells and serum IL-21 were significantly increased in CHC patients. Moreover, circulating CD4＋CXCR5＋ T cells from CHC patients induced higher expressions of CD86 and CD95 in CD27＋IgG＋ B cells in a co-culture system; the blockade of the IL-21 decreased the expression levels of CD86 and CD95 in CD27＋IgG＋ B cells.CONCLUSIONS： HCV infection increased the frequency of CD4＋CXCR5＋ T cells and decreased the frequency of CD27＋IgG＋ B cells. CD4＋CXCR5＋ T cells activated CD27＋IgG＋ B cells via the secretion of IL-21.展开更多
Background: The programmed cell death-1(PD-1)/programmed cell death-ligand 1(PD-L1) pathway inhibits the activation of T cells and plays a crucial role in the negative regulation of cellular and humoral immune respons...Background: The programmed cell death-1(PD-1)/programmed cell death-ligand 1(PD-L1) pathway inhibits the activation of T cells and plays a crucial role in the negative regulation of cellular and humoral immune responses.Diffuse large B-cell lymphoma(DLBCL) is the most common lymphoid malignancy in adults. In the present study, we aimed to detect the expression of PD-L1 in DLBCL and to analyze its relationship with prognosis.Methods: We reviewed medical records of 204 newly diagnosed DLBCL patients in Sun Yat-sen University Cancer Center between October 2005 and August 2012. The expression of PD-L1 in tumor tissues from these 204 patients was detected using immunohistochemical(IHC) assay. The expression of anaplastic lymphoma kinase(ALK), CD5,CD30, and C-Myc in tumor specimens from 109 patients was detected using IHC, and Epstein-Barr virus(EBV)-encoded RNAs(EBERs) were detected using fluorescence in situ hybridization. The Spearman method was used for correlation analysis. The Kaplan-Meier method with log-rank test was used for univariate analysis. Cox proportional hazards model was used for multivariate analysis.Results: Of the 204 patients, 100(49.0%) were PD-L1-positive in tumor cells and 44(21.6%) were PD-L1-positive in tumor microenvironment. PD-L1 expression in tumor cells and tumor microenvironment were more common in the non-germinal center B-cell-like(GCB) subtype than in the GCB subtype(P = 0.02 and P= 0.04). Patients with PD-L1 expression in tumor microenvironment were more likely to be resistant to first-line chemotherapy when compared with the patients without PD-L1 expression in tumor microenvironment(P = 0.03). PD-L1 expression in tumor microenvironment was negatively correlated with C-Myc expression(r =-0.20, P = 0.04). No correlations were detected between PD-L1 expression and the expression of ALK, CD5, and CD30 as well as EBERs. The 5-year overall survival(OS)rates were 50.0% and 67.3% in patients with and without PD-L1 expression in tumor cells(P = 0.02). PD-L1 expression in tumor cells was an independent risk predictor for OS(P < 0.01).Conclusions: PD-L1 expression is more common in the non-GCB subtype than in the GCB subtype. PD-L1 expression in tumor microenvironment has a negative correlation with C-Myc. PD-L1 positivity predicts short survival in DLBCL patients. For patients with PD-L1 expression, more strategy such as anti-PD-L1 antibody treatment should be recommended.展开更多
Background: Circulating microRNAs are potential biomarkers of diagnostic and prognostic impact in various inflammatory and malignant diseases. Aim: Linking inflammation with malignancy, we studied miRNA-21 in sera of ...Background: Circulating microRNAs are potential biomarkers of diagnostic and prognostic impact in various inflammatory and malignant diseases. Aim: Linking inflammation with malignancy, we studied miRNA-21 in sera of hepatitis-C-virus (HCV) and none hepatitis diffuse large B-cell lymphoma (DLBCL) patients, aiming to identify its differential expression and prognosis in DLBCL with its subtypes;germinal center B-cell (GCB) and activated B-cell-like (ABC) and to evaluate its relation with HCV. Subjects and Methods: MiRNA-21 expression was measured using TaqMan quantitative RT-PCR in sera of 30 newly diagnosed DLBCL patients (HCV positive (n = 10), HCV negative (n = 20)) and 20 controls (HCV positive (n = 10), HCV negative (n = 10)). Results: MiRNA-21 expression was significantly higher in DLBCL patients than in control (p = 0.00). Significant positive correlations between miRNA-21 and LDH, IPI and disease stage were detected (p Conclusion: Our study shows that miRNA-21 is over expressed in our patients with DLBCL, displaying higher levels in ABC than in GCB subtypes. MiRNA-21 is associated with poor response to treatment and survival in DLBCL. MiRNA-21 is a potential marker of necro-inflammation independent of its role in tumorogenesis, showing higher expression in HCV positive DLBCL patients compared to none hepatitis patients.展开更多
AIM:To evaluate if indolent B cell-non Hodgkin's lymphoma(B-NHL) and diffuse large B-cell lymphoma(DLBCL) in hepatitis C virus(HCV) positive patients could have different biological and clinical characteristics re...AIM:To evaluate if indolent B cell-non Hodgkin's lymphoma(B-NHL) and diffuse large B-cell lymphoma(DLBCL) in hepatitis C virus(HCV) positive patients could have different biological and clinical characteristics requiring different management strategies.METHODS:A group of 24 HCV related B-NHL patients(11 indolent,13 DLBCL) in whom the biological and clinical characteristics were described and confronted.Patients with DLBCL were managed with the standard of care of treatment.Patients with indolent HCV-related B-NHL were managed with antiviral treatment pegylated interferon plus ribavirin and their course observed.The outcomes of the different approaches were compared.RESULTS:Patients with DLBCL had a shorter duration of HCV infection and a higher prevalence of HCV genotype 1 compared to patients with indolent B-NHL in which HCV genotype 2 was the more frequent genotype.Five of the 9 patients with indolent HCV-relatedB-NHL treated with only antiviral therapy,achieved a complete response of their onco-haematological disease(55%).Seven of the 13 DLBCL patients treated with immunochemotheraphy obtained a complete response(54%).CONCLUSION:HCV genotypes and duration of HCV infection differed between B-NHL subtypes.Indolent lymphomas can be managed with antiviral treatment,while DLBCL is not affected by the HCV infection.展开更多
Background: Members of the NFκB [p65] family have potential diagnostic and prognostic role in various inflammatory diseases and Lymphomas. Aim: We studied NFκB [p65] in paraffin blocks of hepatitis-C-virus [HCV] pos...Background: Members of the NFκB [p65] family have potential diagnostic and prognostic role in various inflammatory diseases and Lymphomas. Aim: We studied NFκB [p65] in paraffin blocks of hepatitis-C-virus [HCV] positive genotype-4 and HCV negative diffuse large B-cell lymphoma [DLBCL] patients, aiming at identification of its differential expression and prognosis in DLBCL and its subtypes;GCB and ABC. This is to establish its relation to HCV infection and its role in lymphogenesis. Besides assessing the role of new directly acting antiviral drugs [Sofusbuvir/Ledipasvir] concomitantly administered to [CHOP] combination in HCV positive DLBCL. Subjects and Methods: NFκB [p65] expression was assessed using Anti-NFκB [p65] antibody semi-quantitative technique in 30 newly diagnosed DLBCL patients [HCV positive [n = 15], HCV negative [n = 15]. Results: NFκB [p65] expression was higher in the HCV positive DLBCL patients than their HCV negative counterpart, with a positive correlation with the viral load [r = 0.536, p = 0.088]. NFκB [p65] expression was significantly more frequently detected in the ABC subtype than GCB subtype [p = 0.04]. Patients who expressed NFκB [p65] had higher incidence of extranodal involvement, advanced stages, higher LDH levels and IPI score. Besides, the expression of NFκB [P65] revealed an inferior overall response [OR] [p = 0.044]. Higher complete response rates to CHOP concomitantly with antiviral [ledipasvir/sofosbuvir] were encountered in the HCV positive group. In HCV positive group, NFκB [P65] displayed a positive relationship with the viral load and liver enzymes [p = 0.04], besides an inverse relation with serum albumin. This raises the possibility that NFκB [p65] expression is suggestive of the hepatic necro-inflammation in HCV patients. The ABC group presented more in advanced stages than GCB. Higher frequency of the ABC subgroup exhibited intermediate to high viral load, while it was less in the GCB. A statistically significant difference was found in the NFκB [p65] positive patients as regards MUM1 expression among the two groups [p ≤ 0.001]. Double positive [CD10+, MUM1+] and triple negative [CD10-, BCL6-, MUM1-] cases were encountered in the HCV positive group, and were characterized with a high NFκB [p65] expression. Conclusion: NFκB [p65] is expressed in patients with DLBCL, more frequently in ABC than in GCB subtypes. Expression of NFκB [p65] is associated with poor response to therapy in DLBCL. The NFκB [p65] disclosed an increased expression in HCV positive DLBCL compared to HCV negative group. The viral load displayed a positive correlation with the NFκB [p65] expression. Simultaneous administration of DAAs in combination with CHOP disclosed a better response and high tolerability.展开更多
基金supported by grants from the National Science and Technology Major Project for Infectious Diseases Control during the 11th Five-Year Plan(2008ZX10002-012 and 2008ZX10002-013)the 12th Five-Year Plan(2012ZX10002003)
文摘BACKGROUND： Chronic hepatitis C virus （HCV） infection causes the skewing and activation of B cell subsets, but the characteristics of IgG＋ B cells in patients with chronic hepa- titis C （CHC） infection have not been thoroughly elucidated. CD4＋CXCR5＋ follicular helper T （Tfh） cells, via interleukin （IL）-21 secretion, activate B cells. However, the role of CD4＋CXCR5＋ T cells in the activation ofIgG＋ B cells in CHC patients is not clear. METHODS： The frequency of IgG＋ B cells, including CD27-IgG＋ B and CD27＋IgG＋ B cells, the expression of the activation markers （CD86 and CD95） in IgG＋ B cells, and the percentage of circu- lating CD4＋CXCR5＋ T cells were detected by flow cytometry in CHC patients （n=70） and healthy controls （n=25）. The con- centrations of serum IL-21 were analyzed using ELISA. The role of CD4＋CXCR5＋ T cells in the activation of IgG＋ B cells was investigated using a co-culture system. RESULTS： A significantly lower proportion of CD27＋IgG＋ B cells with increased expression of CD86 and CD95 was observed in CHC patients. The expression of CD95 was negatively correlated with the percentage of CD27＋IgG＋ B cells, and it contributed to CD27＋IgG＋ B cell apoptosis. Circulating CD4＋CXCR5＋ T cells and serum IL-21 were significantly increased in CHC patients. Moreover, circulating CD4＋CXCR5＋ T cells from CHC patients induced higher expressions of CD86 and CD95 in CD27＋IgG＋ B cells in a co-culture system; the blockade of the IL-21 decreased the expression levels of CD86 and CD95 in CD27＋IgG＋ B cells.CONCLUSIONS： HCV infection increased the frequency of CD4＋CXCR5＋ T cells and decreased the frequency of CD27＋IgG＋ B cells. CD4＋CXCR5＋ T cells activated CD27＋IgG＋ B cells via the secretion of IL-21.
基金supported by National Natural Science Foundation of China(Nos.81672686,81372883,and 81001052)Natural Science Foundation of Guangdong Province,China(No.2015A030313020)+2 种基金Science and Technology Planning Project of Guangdong Province,China(No.2011B031800222)Young Talents Key Project of Sun Yat-sen University(No.2015ykzd13)the Sister Institution Network Fund of MD Anderson Cancer Center
文摘Background: The programmed cell death-1(PD-1)/programmed cell death-ligand 1(PD-L1) pathway inhibits the activation of T cells and plays a crucial role in the negative regulation of cellular and humoral immune responses.Diffuse large B-cell lymphoma(DLBCL) is the most common lymphoid malignancy in adults. In the present study, we aimed to detect the expression of PD-L1 in DLBCL and to analyze its relationship with prognosis.Methods: We reviewed medical records of 204 newly diagnosed DLBCL patients in Sun Yat-sen University Cancer Center between October 2005 and August 2012. The expression of PD-L1 in tumor tissues from these 204 patients was detected using immunohistochemical(IHC) assay. The expression of anaplastic lymphoma kinase(ALK), CD5,CD30, and C-Myc in tumor specimens from 109 patients was detected using IHC, and Epstein-Barr virus(EBV)-encoded RNAs(EBERs) were detected using fluorescence in situ hybridization. The Spearman method was used for correlation analysis. The Kaplan-Meier method with log-rank test was used for univariate analysis. Cox proportional hazards model was used for multivariate analysis.Results: Of the 204 patients, 100(49.0%) were PD-L1-positive in tumor cells and 44(21.6%) were PD-L1-positive in tumor microenvironment. PD-L1 expression in tumor cells and tumor microenvironment were more common in the non-germinal center B-cell-like(GCB) subtype than in the GCB subtype(P = 0.02 and P= 0.04). Patients with PD-L1 expression in tumor microenvironment were more likely to be resistant to first-line chemotherapy when compared with the patients without PD-L1 expression in tumor microenvironment(P = 0.03). PD-L1 expression in tumor microenvironment was negatively correlated with C-Myc expression(r =-0.20, P = 0.04). No correlations were detected between PD-L1 expression and the expression of ALK, CD5, and CD30 as well as EBERs. The 5-year overall survival(OS)rates were 50.0% and 67.3% in patients with and without PD-L1 expression in tumor cells(P = 0.02). PD-L1 expression in tumor cells was an independent risk predictor for OS(P < 0.01).Conclusions: PD-L1 expression is more common in the non-GCB subtype than in the GCB subtype. PD-L1 expression in tumor microenvironment has a negative correlation with C-Myc. PD-L1 positivity predicts short survival in DLBCL patients. For patients with PD-L1 expression, more strategy such as anti-PD-L1 antibody treatment should be recommended.
文摘Background: Circulating microRNAs are potential biomarkers of diagnostic and prognostic impact in various inflammatory and malignant diseases. Aim: Linking inflammation with malignancy, we studied miRNA-21 in sera of hepatitis-C-virus (HCV) and none hepatitis diffuse large B-cell lymphoma (DLBCL) patients, aiming to identify its differential expression and prognosis in DLBCL with its subtypes;germinal center B-cell (GCB) and activated B-cell-like (ABC) and to evaluate its relation with HCV. Subjects and Methods: MiRNA-21 expression was measured using TaqMan quantitative RT-PCR in sera of 30 newly diagnosed DLBCL patients (HCV positive (n = 10), HCV negative (n = 20)) and 20 controls (HCV positive (n = 10), HCV negative (n = 10)). Results: MiRNA-21 expression was significantly higher in DLBCL patients than in control (p = 0.00). Significant positive correlations between miRNA-21 and LDH, IPI and disease stage were detected (p Conclusion: Our study shows that miRNA-21 is over expressed in our patients with DLBCL, displaying higher levels in ABC than in GCB subtypes. MiRNA-21 is associated with poor response to treatment and survival in DLBCL. MiRNA-21 is a potential marker of necro-inflammation independent of its role in tumorogenesis, showing higher expression in HCV positive DLBCL patients compared to none hepatitis patients.
文摘AIM:To evaluate if indolent B cell-non Hodgkin's lymphoma(B-NHL) and diffuse large B-cell lymphoma(DLBCL) in hepatitis C virus(HCV) positive patients could have different biological and clinical characteristics requiring different management strategies.METHODS:A group of 24 HCV related B-NHL patients(11 indolent,13 DLBCL) in whom the biological and clinical characteristics were described and confronted.Patients with DLBCL were managed with the standard of care of treatment.Patients with indolent HCV-related B-NHL were managed with antiviral treatment pegylated interferon plus ribavirin and their course observed.The outcomes of the different approaches were compared.RESULTS:Patients with DLBCL had a shorter duration of HCV infection and a higher prevalence of HCV genotype 1 compared to patients with indolent B-NHL in which HCV genotype 2 was the more frequent genotype.Five of the 9 patients with indolent HCV-relatedB-NHL treated with only antiviral therapy,achieved a complete response of their onco-haematological disease(55%).Seven of the 13 DLBCL patients treated with immunochemotheraphy obtained a complete response(54%).CONCLUSION:HCV genotypes and duration of HCV infection differed between B-NHL subtypes.Indolent lymphomas can be managed with antiviral treatment,while DLBCL is not affected by the HCV infection.
文摘Background: Members of the NFκB [p65] family have potential diagnostic and prognostic role in various inflammatory diseases and Lymphomas. Aim: We studied NFκB [p65] in paraffin blocks of hepatitis-C-virus [HCV] positive genotype-4 and HCV negative diffuse large B-cell lymphoma [DLBCL] patients, aiming at identification of its differential expression and prognosis in DLBCL and its subtypes;GCB and ABC. This is to establish its relation to HCV infection and its role in lymphogenesis. Besides assessing the role of new directly acting antiviral drugs [Sofusbuvir/Ledipasvir] concomitantly administered to [CHOP] combination in HCV positive DLBCL. Subjects and Methods: NFκB [p65] expression was assessed using Anti-NFκB [p65] antibody semi-quantitative technique in 30 newly diagnosed DLBCL patients [HCV positive [n = 15], HCV negative [n = 15]. Results: NFκB [p65] expression was higher in the HCV positive DLBCL patients than their HCV negative counterpart, with a positive correlation with the viral load [r = 0.536, p = 0.088]. NFκB [p65] expression was significantly more frequently detected in the ABC subtype than GCB subtype [p = 0.04]. Patients who expressed NFκB [p65] had higher incidence of extranodal involvement, advanced stages, higher LDH levels and IPI score. Besides, the expression of NFκB [P65] revealed an inferior overall response [OR] [p = 0.044]. Higher complete response rates to CHOP concomitantly with antiviral [ledipasvir/sofosbuvir] were encountered in the HCV positive group. In HCV positive group, NFκB [P65] displayed a positive relationship with the viral load and liver enzymes [p = 0.04], besides an inverse relation with serum albumin. This raises the possibility that NFκB [p65] expression is suggestive of the hepatic necro-inflammation in HCV patients. The ABC group presented more in advanced stages than GCB. Higher frequency of the ABC subgroup exhibited intermediate to high viral load, while it was less in the GCB. A statistically significant difference was found in the NFκB [p65] positive patients as regards MUM1 expression among the two groups [p ≤ 0.001]. Double positive [CD10+, MUM1+] and triple negative [CD10-, BCL6-, MUM1-] cases were encountered in the HCV positive group, and were characterized with a high NFκB [p65] expression. Conclusion: NFκB [p65] is expressed in patients with DLBCL, more frequently in ABC than in GCB subtypes. Expression of NFκB [p65] is associated with poor response to therapy in DLBCL. The NFκB [p65] disclosed an increased expression in HCV positive DLBCL compared to HCV negative group. The viral load displayed a positive correlation with the NFκB [p65] expression. Simultaneous administration of DAAs in combination with CHOP disclosed a better response and high tolerability.
文摘目的分析体质量指数(Body mass index,BMI)与老年慢性心力衰竭(Chronic heart failure,CHF)患者血浆胱抑素C(cystatinC,Cys-C)、N末端B型利钠肽原(N-terminal pro-B-type natriuretic peptide,NT-proBNP)水平相关性,并分析血浆Cys-C、NT-proBNP评估老年CHF患者预后价值。方法选择2021年7月—2022年10月在本院接受治疗的192例老年慢性心力衰竭(CHF)患者作为研究对象,按照BMI指数分为肥胖组(49例)、超重组(68例)和正常组(75例)三组。对比各亚组患者血浆Cys-C、NT-proBNP水平差异,采用Pearson相关性分析的方式探究老年CHF患者BMI指数与血浆Cys-C、NT-proBNP相关性,对入组患者实施12个月随访,将患者按照预后情况区分为死亡组和存活组,对比两亚组患者血浆Cys-C、NT-proBNP水平差异并评估预后评估价值。结果肥胖组患者血浆Cys-C、NT-proBNP水平高于超重组,超重组患者血浆Cys-C、NT-proBNP水平高于正常组,差异具有统计学意义(P<0.05);入组老年CHF患者的BMI指数与其血浆Cys-C、NT-proBN水平均呈现明显的正相关性(r=0.7104,P<0.0001)(r=0.6603,P<0.0001);随访12个月显示,死亡组患者的血浆Cys-C、NT-proBNP水平显著高于存活组患者,差异具有统计学意义(P<0.05);血浆Cys-C、NT-proBNP对老年CHF预后评估曲线下面积(area under curv,AUC)为0.6930(P=0.0009)、0.7982(P<0.0001)。结论老年CHF患者随BMI指数升高,血浆Cys-C、NT-proBNP水平逐渐升高,血浆Cys-C、NT-proBNP对老年CHF临床结局具有一定的预测价值,进一步研究有推广应用于老年CHF预后评估潜力。
