RESUMO
Continuous-variable quantum key distribution (CVQKD) holds an advantage of well compatibility with classical coherent optical communications. However, there exists a performance trade-off between CVQKD and classical communication on single-mode fiber (SMF) because of the spontaneous Raman scattering. Space-division multiplexing (SDM) technique may provide a feasible way to mitigate this performance trade-off in short-distance communication while CVQKD coexisting with classical signals on few-mode fiber (FMF). Here, we examine the feasibility of CVQKD coexisting with classical signals on FMF and analyze the noise impact in weak coupling regime. We find that the inter-mode crosstalk generated from the mode coupling and re-coupling between modes and the group delay spread originated from the differential group delay (DGD) contribute the main noise sources. DGD may become one of the main limits for FMF-based CVQKD towards high-speed system. In addition, a well channel wavelength management is needed to suppress the inter-mode four-wave-mixing for achieving the positive secret key rates. The numerical simulations identify the key parameters for CVQKD system, enabling a helpful insight for realizing security analysis of the Gaussian modulated coherent state protocol. It shows that CVQKD coexisting with high power classical signals on FMF is feasible to implement with standard telecommunication components and able to operate at higher secret key rates. The results may provide a potential guideline for the practical high-rate CVQKD integrating with the FMF-based configuration.
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Underwater quantumkey distribution (QKD) is tough but important formodern underwater communications in an insecure environment. It can guarantee secure underwater communication between submarines and enhance safety for critical network nodes. To enhance the performance of continuous-variable quantumkey distribution (CVQKD) underwater in terms ofmaximal transmission distance and secret key rate as well, we adopt measurement-device-independent (MDI) quantum key distribution with the zero-photon catalysis (ZPC) performed at the emitter of one side, which is the ZPC-based MDI-CVQKD. Numerical simulation shows that the ZPC-involved scheme, which is a Gaussian operation in essence, works better than the single photon subtraction (SPS)-involved scheme in the extreme asymmetric case. We find that the transmission of the ZPC-involved scheme is longer than that of the SPS-involved scheme. In addition, we consider the effects of temperature, salinity and solar elevation angle on the system performance in pure seawater. The maximal transmission distance decreases with the increase of temperature and the decrease of sunlight elevation angle, while it changes little over a broad range of salinity.
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BACKGROUND: A considerable proportion of autoimmune hemolytic anemia (AIHA) are secondary to underlying autoimmune disorders, especially syetemic lupus erythematosus (SLE), and the clinical and laboratory index for early discrimination between primary and SLE-related AIHA has yet to be defined. In the present study, we proposed novel cytokine patterns in the pathogenesis of AIHA as well as parameters for the timely identification of SLE-related patients. METHODS: AIHA patients confirmed by immunohematology techniques from September 2010 to December 2012 in our facility were consecutively included and categorized into primary (n = 19) and SLE-related (n = 18) groups. Plasma cytokine profiles were measured in a single procedure by Quantibody Human Inflammatory Array 1 (RayBiotech, Norcross, GA). RESULTS: SLE-related AIHA patients demonstrated younger age (39 ± 20 vs.57 ± 16 years, p = 0.004), poorer reticulocyte compensation (6.8 ± 7.1 vs.12.2 ± 8.6%, p = 0.045), lower levels of lactate dehydrogenase [361 (265-498) vs. 622 (387-1154) U/L, p = 0.004], and higher occurrence of anticardiolipin antibody [9/18 (50%) vs. 2/19 (10.9%), p = 0.009]. MCP-1/CCL2, MIP-1ß/CCL4, BLC/CXCL13, IL-8/CXCL8, sTNFRI, and sTNFRII were significantly up-regulated in both groups, while sTNFRII was remarkably higher in SLE-related patients. Among both groups, hemoglobin level was negatively correlated with CXCL13 (r = -0.332, p = 0.044), while reticulocyte count was positively correlated with CCL4 (r = 0.456, p = 0.005). CONCLUSION: CXCL13 and CCL4 could act as circulating biomarkers in AIHA, and indicated disease severity and erythroid compensation, respectively. Higher plasma sTNFRII might favor the diagnosis of SLE-related instead of primary AIHA.
Assuntos
Anemia Hemolítica Autoimune/sangue , Quimiocina CCL4/sangue , Quimiocina CXCL13/sangue , Citocinas/sangue , Mediadores da Inflamação/metabolismo , Lúpus Eritematoso Sistêmico/sangue , Receptores Tipo II do Fator de Necrose Tumoral/sangue , Receptores Tipo I de Fatores de Necrose Tumoral/sangue , Adulto , Anemia Hemolítica Autoimune/complicações , Biomarcadores/sangue , Feminino , Hemoglobinas/metabolismo , Humanos , Lúpus Eritematoso Sistêmico/complicações , Masculino , Pessoa de Meia-Idade , SolubilidadeRESUMO
BACKGROUND & AIMS: Thrombocytopaenia is a frequent feature in patients with HBV-related liver disease. Its underlying mechanism is not fully understood. Multiple factors might contribute to the development of thrombocytopaenia. In this study, we investigated the reticulated platelets (RP), glycocalicin (GC), serum thrombopoietin (TPO) and platelet glycoprotein (GP) in different stages of the disease. METHODS: One hundred and fourteen patients with HBV-related liver disease (30 with chronic hepatitis B (CHB), 20 patients in Child A without thrombocytopaenia, 19 patients in Child A with thrombocytopaenia, 45 in Child B/C with thrombocytopaenia) and 25 normal controls (NC) were enrolled. Liver cirrhosis (LC) was classified according to modified Child-Turcotte-Pugh (CTP) score. Serum TPO levels and GC were measured by ELISA. RP and platelet glycoprotein (GP) expression were detected by flow cytometry. RESULTS: The TPO levels of patients with LC were significantly lower than that of controls, even in patients of Child A without thrombocytopaenia group. Serum TPO level was positively correlated (r = 0.65, p < 0.01) with serum albumin in Child B/C group. Both the RP percentages and the glycocalicin index (GCI) levels were significantly higher in patients groups including CHB and Child A without thrombocytopaenia than that of normal controls. A negative correlation existed in HBV DNA copies and the GPs% in patients with CHB and Child A without thrombocytopaenia. CONCLUSION: Abnormal platelet production, destruction and platelet-specific glycoproteins levels were detected before the occurrence of thrombocytopaenia in HBV-related liver disease, indicating that multiple mechanisms might play roles in thrombocytopaenia in HBV-infected patients.
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Plaquetas/citologia , Hepatite B/complicações , Complexo Glicoproteico GPIb-IX de Plaquetas/metabolismo , Glicoproteínas da Membrana de Plaquetas/metabolismo , Trombocitopenia/etiologia , Trombocitopenia/metabolismo , Trombopoetina/sangue , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , HumanosRESUMO
Primary immune thrombocytopenia (ITP) is an autoimmune heterogeneous disorder that is characterized by decreased platelet count. The interleukin-23 receptor (IL-23R) has been identified as a susceptibility gene for the development of multiple autoimmune diseases. To investigate the possible association of IL-23R gene single-nucleotide polymorphisms (SNPs) with ITP and the association with the clinical outcome of pulsed high-dose dexamethasone (HD-DXM) therapy, four SNPs in the IL-23R gene, rs10889677, rs1884444, rs7517847, and rs11209032, were tested in a cohort of 75 ITP subjects and 81 controls by direct sequencing. IL-23R rs1884444 GT/TT variant genotypes were observed to be associated with significantly increased risk of ITP as compared with controls (GT/TT vs. GG: odds ratio (OR) 2.776, 95 % confidence intervals (CI) 1.086-7.090, p = 0.028). However, other three SNPs revealed no statistically significant differences between patients and controls (rs10889677 CA/AA vs. CC: OR 2.200, 95 % CI 0.727-6.661, p = 0.155; rs11209032 GA/AA vs. GG: OR 0.747, 95 % CI 0.379-1.472, p = 0.399; rs7517847 TG/GG vs. TT: OR 1.031, 95 % CI 0.544-1.956, p = 0.925). Furthermore, IL-23R SNPs revealed no association with clinical outcome of HD-DXM therapy. This study suggests that polymorphism in the IL-23R gene, rs1884444, indicates a significant association with susceptibility to ITP in a recessive genetic model but does not have association with the clinical outcome of HD-DXM therapy.
Assuntos
Dexametasona/uso terapêutico , Polimorfismo de Nucleotídeo Único , Púrpura Trombocitopênica Idiopática/genética , Receptores de Interleucina/genética , Adolescente , Adulto , Idoso , China/epidemiologia , Dexametasona/administração & dosagem , Relação Dose-Resposta a Droga , Etnicidade/genética , Feminino , Frequência do Gene , Genes Recessivos , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Púrpura Trombocitopênica Idiopática/epidemiologia , Púrpura Trombocitopênica Idiopática/etnologia , Receptores de Interleucina/fisiologia , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: B cells expressing CD5 are potentially capable of producing interleukin 10 (IL-10) which contributes to the regulatory function of B cells. This study was aimed at exploring the alteration of numbers of CD5(+) B cells and their ability of producing IL-10 in patients with immune thrombocytopenia (ITP), and the effects of pulsed high-dose dexamethasone (HD-DXM) therapy on CD5(+) B cells. METHODS: Peripheral blood mononuclear cells from 25 adult ITP patients were stained with PE-CD5/FITC-CD19 antibodies for flow cytometry analyses before and after HD-DXM therapy. The expression of IL-10 mRNA was measured by RT-PCR. After 24 h culture with or without dexamethasone in the presence of PMA, ionomycin and Brefeldin A, cells were permeabilized and stained with APC-IL-10 antibody to investigate intracellular IL-10 expression. Supernatant IL-10 concentration was detected by ELISA. RESULTS: The number of CD5(+) B cells was elevated in patients with ITP. Expression of IL-10 mRNA, percentage of IL-10(+) cells and intracellular IL-10 in CD5(+) B cells from untreated patients were significantly higher than that in controls. In contrast, ITP patients showed lower IL-10 concentration in supernatants than controls. After HD-DXM therapy, the number of CD5(+) B cells decreased to normal level, while intracellular IL-10 expression in CD5(+) B cells was further enhanced and IL-10 concentration in supernatants was also increased. Similar results were observed when dexamethasone was administrated in vitro. CONCLUSIONS: Increased number of CD5(+) B cells in which IL-10 is accumulated with decreased IL-10 concentration in supernatants suggests that the ability of CD5(+) B cells to secret IL-10 is impaired in ITP patients. Both the aberrant number and ability of IL-10 secretion of CD5(+) B cells could be corrected by HD-DXM.
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Anti-Inflamatórios/uso terapêutico , Linfócitos B/efeitos dos fármacos , Dexametasona/uso terapêutico , Interleucina-10/metabolismo , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Adulto , Idoso , Anti-Inflamatórios/farmacologia , Linfócitos B/imunologia , Linfócitos B/patologia , Antígenos CD5/genética , Antígenos CD5/imunologia , Células Cultivadas , Dexametasona/farmacologia , Esquema de Medicação , Feminino , Citometria de Fluxo , Expressão Gênica/efeitos dos fármacos , Humanos , Interleucina-10/genética , Interleucina-10/imunologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Púrpura Trombocitopênica Idiopática/genética , Púrpura Trombocitopênica Idiopática/imunologia , Púrpura Trombocitopênica Idiopática/patologia , RNA Mensageiro/genética , RNA Mensageiro/imunologiaRESUMO
Gastrointestinal diffuse large B cell lymphoma (DLBCL) is a common subtype of extranodal lymphoma. There has been uncertainty about the clinical efficacy of combination therapy (surgery and chemotherapy) for gastrointestinal DLBCL. We retrospectively analyzed 114 patients with newly diagnosed gastrointestinal DLBCL from six medical centers. We evaluated four groups based on whether they were treated with or without surgery as the initial treatment for DLBCL, followed by either a regimen with cyclophosphamide, vincristine, doxorubicin, and prednisone (CHOP) or CHOP with rituximab (R-CHOP). For all patients, treatment with R-CHOP resulted in significantly greater overall survival (OS; 93.2 vs. 74.5%, p = 0.008) and progression-free survival (89.8% vs. 72.7, p = 0.029). Tumor resection did not improve OS (84.0 vs. 85.0%, for surgery and chemotherapy alone, respectively, p = 0.980). However, for younger patients, overall survival was greater (p = 0.005) for patients treated with surgery plus chemotherapy (83.9%) than for patients treated with chemotherapy alone (40.0%). Elevated serum lactate dehydrogenase level (p = 0.004) and performance status (Eastern Cooperative Oncology Group; p = 0.003) were independent predictors of survival in patients with gastrointestinal DLBCL. Stage-modified IPI was recognized as the best prognostic tool. There were significant differences among patients with low-risk, intermediate-risk, and high-risk groups in 50-month OS (94.2 vs. 84.0 vs. 66.7%, p = 0.008). The results of this large-scale study suggest that R-CHOP regimen is the first-line treatment for gastrointestinal DLBCL. The benefit of surgery for these patients remains controversial. Further prospective analyses are warranted.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Medicina Baseada em Evidências , Neoplasias Gastrointestinais/diagnóstico , Neoplasias Gastrointestinais/tratamento farmacológico , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Adolescente , Adulto , Idoso , Anticorpos Monoclonais Murinos/administração & dosagem , Anticorpos Monoclonais Murinos/uso terapêutico , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , China , Terapia Combinada , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Seguimentos , Neoplasias Gastrointestinais/etnologia , Neoplasias Gastrointestinais/cirurgia , Humanos , Linfoma Difuso de Grandes Células B/etnologia , Linfoma Difuso de Grandes Células B/cirurgia , Masculino , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Prognóstico , Estudos Retrospectivos , Rituximab , Análise de Sobrevida , Vincristina/uso terapêutico , Adulto JovemRESUMO
The purpose of the study is to evaluate the 10 years follow-up of the efficacy in Chinese patients receiving cyclophosphamide, doxorubicin/epirubicin, vincristine, and prednisone (CHOP) or rituximab plus CHOP (R-CHOP) regimen as the initial treatment for diffuse large B cell lymphoma (DLBCL). We have retrospectively analyzed 437 patients with DLBCL who were newly diagnosed and received CHOP or R-CHOP regimen in six university hospitals and closely followed up after the completion of treatment. For all patients, there were significant differences between R-CHOP and CHOP for overall survival (OS) (median follow-up 86 months, 84.1% vs 70.2%, p = 0.018) and progression-free survival (PFS) (81.5% vs 66.7%, p = 0.015), while elder patients (>60 years old) received higher OS (median follow-up 66 months, 80.7% vs 53.0%, p = 0.011). But for younger patients (≤60 years old), the treatments with rituximab did not demonstrate a significant effect on OS (85.5% vs 79.4%, p = 0.428). In the R-CHOP group, International Prognostic Index (IPI) distinguished three risk groups instead of four risk groups. But in the CHOP group, IPI still distinguished four risk groups. Furthermore, for 212 of 437 patients diagnosed with extranodal involvement DLBCL, R-CHOP regimen provided a longer OS than CHOP regimen did (OS, 89.9% vs 71.7%, p = 0.014). Moreover, patients with extranodal lymphoma had a significant longer survival in rituximab era (OS, 89.9% vs 79.2% for extranodal and nodal, respectively; p = 0.048). The results of this large-scale study suggested that R-CHOP provided a greater survival benefit in the initial treatment of DLBCL. As for the patients with extranodal lymphoma, R-CHOP was also a good choice as first-line treatment. Extranodal disease seems to be an independent good prognostic factor in rituximab era.
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Anticorpos Monoclonais Murinos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Linfoma Difuso de Grandes Células B/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , China , Estudos de Coortes , Terapia Combinada , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Seguimentos , Hematologia/organização & administração , Humanos , Imunoterapia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Oncologia/organização & administração , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Estudos Retrospectivos , Rituximab , Sociedades Médicas , Análise de Sobrevida , Fatores de Tempo , Vincristina/administração & dosagemRESUMO
Frequent mutations in the isocitrate dehydrogenase 1 and 2 genes (IDH1 and IDH2) have been identified in gliomas and acute myeloid leukemia (AML). Our aim is to assess whether IDH mutations were presented in Chinese patients with various hematological disorders. In this study, we screened the IDH1 and IDH2 mutations in a cohort of 456 Chinese patients with various hematological malignancies and disorders. We found three missense (p.R132C, p.R132G, and p.I99M; occurred in five patients) and one silent mutation (c.315C>T; occurred in two patients) in the IDH1 gene and two missense mutations (p.R140Q and p.R172K; occurred in four AML patients) and one silent mutation (c.435G>A) in the IDH2 gene. Except for one non-Hodgkin lymphoma (NHL) patient harboring IDH1 mutation p.R132C, all IDH1 and IDH2 missense mutations were observed in patients with AML. Intriguingly, the IDH2 mutation p.R140Q and novel IDH1 mutation p.I99M co-occurred in a 75-year-old patient with AML developed from myelodysplastic syndromes (MDS). The frequency of IDH1 and IDH2 missense mutations in Chinese AML patients reached 5.9% and 8.3%, respectively. Our results supported the recent findings that IDH gene mutations were common in AML. Conversely, IDH mutations were rather rare in Chinese patients with other types of hematological disorders.
Assuntos
Isocitrato Desidrogenase/genética , Leucemia Mieloide Aguda/genética , Povo Asiático/genética , Estudos de Coortes , Doenças Hematológicas/genética , Humanos , Mutação , Mutação de Sentido IncorretoRESUMO
BACKGROUND: Reactivation of hepatitis B virus (HBV) is less common in lymphoma patients with prior resolved HBV infection [characterized by hepatitis B surface antigen (HBsAg)-negative/hepatitis B core antibody (HBcAb)-positive status] compared with chronic HBV infection (HBsAg positive) when receiving chemotherapy alone. The use of rituximab in chemotherapy regimen might increase the risk of HBV reactivation in patients with prior resolved HBV infection. However, the incidence of HBV reactivation is uncertain, and prophylactic antiviral treatment for this group of patients during rituximab-containing chemotherapy is controversial. The objective of this study was to determine the incidence of HBV reactivation in HBsAg-negative/HBcAb-positive patients diagnosed of diffuse large B-cell lymphoma (DLBCL) and treated with CHOP-like or RCHOP-like regimen. In addition, this study also aims to explore the relationship of HBV reactivation and HBV serology. METHODS: Patients were identified using data from six university hospitals collected between January 1998 and November 2008. Four hundred and thirty-seven patients with complete data were selected based on the diagnosis of CD20+ DLBCL, availability of HBV serum markers prior to initiation of chemotherapy and during the development of hepatitis, completion of at least four cycles of chemotherapy using CHOP-like or RCHOP-like regimen, and follow-up for at least 6 months after completion of treatment. The characteristics of the HBsAg-negative/HBcAb-positive patients treated with CHOP-like regimen were compared to those treated with RCHOP-like regimen. RESULTS: Eighty-eight patients of the total 437 patients had pretreatment serology of prior resolved hepatitis B, with a prevalence of 20.1%. Among them, 45 patients received CHOP-like regimen while 43 patients received RCHOP-like regimen. Five patients developed hepatitis during treatment, two from CHOP group and three from RCHOP group. Only one patient treated with RCHOP had hepatitis associated with HBV reactivation, while the other four patients did not have evidence of HBV reactivation. Those four patients also demonstrated positive HBsAb at baseline, while the only patient who suffered from HBV reactivation had negative HBsAb status. This patient was successfully treated with antiviral medications. There were no statistically significant risk factors predictive of HBV reactivation. CONCLUSIONS: The present study revealed a low HBV reactivation rate of 2.3% in prior resolved hepatitis B among DLBCL patients undergoing RCHOP-like therapy.
Assuntos
Antígenos de Superfície da Hepatite B/análise , Vírus da Hepatite B/efeitos dos fármacos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/virologia , Ativação Viral/efeitos dos fármacos , Adulto , Idoso , Anticorpos Monoclonais/imunologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Antígenos de Superfície da Hepatite B/imunologia , Vírus da Hepatite B/crescimento & desenvolvimento , Vírus da Hepatite B/isolamento & purificação , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Latência Viral/efeitos dos fármacos , Adulto JovemAssuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Rearranjo Gênico/genética , Proteína de Leucina Linfoide-Mieloide/genética , Proteínas de Fusão Oncogênica/genética , Sarcoma Mieloide/diagnóstico , Sarcoma Mieloide/genética , Adulto , Neoplasias da Mama/complicações , Feminino , Humanos , Sarcoma Mieloide/complicaçõesAssuntos
Doença de Hodgkin/complicações , Imunoglobulina A/análise , Linfoma de Zona Marginal Tipo Células B/complicações , Linfoma Folicular/complicações , Linfoma Difuso de Grandes Células B/complicações , Paraproteinemias/complicações , Idoso , Anticorpos Monoclonais Murinos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Neoplasias Gastrointestinais/sangue , Neoplasias Gastrointestinais/complicações , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/imunologia , Doença de Hodgkin/sangue , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/imunologia , Humanos , Cadeias kappa de Imunoglobulina/análise , Cadeias lambda de Imunoglobulina/análise , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/imunologia , Linfoma de Zona Marginal Tipo Células B/sangue , Linfoma de Zona Marginal Tipo Células B/tratamento farmacológico , Linfoma de Zona Marginal Tipo Células B/imunologia , Linfoma Folicular/sangue , Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/imunologia , Linfoma Difuso de Grandes Células B/sangue , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/imunologia , Masculino , Pessoa de Meia-Idade , Paraproteinemias/sangue , Paraproteinemias/tratamento farmacológico , Paraproteinemias/imunologia , Prednisona/uso terapêutico , Neoplasias da Próstata/sangue , Neoplasias da Próstata/complicações , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/imunologia , Recidiva , Indução de Remissão , Rituximab , Vincristina/uso terapêuticoAssuntos
Imunoglobulina A , Cadeias lambda de Imunoglobulina , Idoso , Glomerulonefrite Membranoproliferativa/sangue , Glomerulonefrite Membranoproliferativa/tratamento farmacológico , Glomerulonefrite Membranoproliferativa/etiologia , Glomerulonefrite Membranoproliferativa/patologia , Glomerulonefrite Membranoproliferativa/urina , Humanos , Masculino , Pessoa de Meia-Idade , Paraproteinemias/sangue , Paraproteinemias/complicações , Paraproteinemias/tratamento farmacológico , Paraproteinemias/patologia , Paraproteinemias/urinaRESUMO
Trace elements play important roles in human health, but little is known about their functions in humoral immunity. Here, we show an important role for iron in inducing cyclin E and B cell proliferation. We find that iron-deficient individuals exhibit a significantly reduced antibody response to the measles vaccine when compared to iron-normal controls. Mice with iron deficiency also exhibit attenuated T-dependent or T-independent antigen-specific antibody responses. We show that iron is essential for B cell proliferation; both iron deficiency and α-ketoglutarate inhibition could suppress cyclin E1 induction and S phase entry of B cells upon activation. Finally, we demonstrate that three demethylases, KDM2B, KDM3B and KDM4C, are responsible for histone 3 lysine 9 (H3K9) demethylation at the cyclin E1 promoter, cyclin E1 induction and B cell proliferation. Thus, our data reveal a crucial role of H3K9 demethylation in B cell proliferation, and the importance of iron in humoral immunity.
Assuntos
Linfócitos B/imunologia , Proliferação de Células , Histonas/química , Histonas/imunologia , Imunidade Humoral , Lisina/imunologia , Animais , Linfócitos B/química , Linfócitos B/citologia , Ciclo Celular , Células Cultivadas , Ciclina E/genética , Ciclina E/imunologia , Desmetilação , Proteínas F-Box/genética , Proteínas F-Box/imunologia , Histonas/genética , Ferro/metabolismo , Histona Desmetilases com o Domínio Jumonji/genética , Histona Desmetilases com o Domínio Jumonji/imunologia , Ativação Linfocitária , Lisina/genética , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Oncogênicas/genética , Proteínas Oncogênicas/imunologia , Regiões Promotoras Genéticas , Linfócitos T/citologia , Linfócitos T/imunologiaRESUMO
: Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by decreased platelet count of which dysfunctional cellular immunity in its pathogenesis. Signal transducer and activator of transcription 3 (STAT3) is critical for the differentiation of T cells. The present study was aimed to investigate the STAT3 protein phosphorylation of CD4 T cells in ITP patients. Fourteen patients of newly diagnosed ITP with complete remission (R group) and other 15 newly diagnosed ITP patients with nonresponse (N group) after corticosteroids therapy were included. Sixteen healthy human volunteers were served as normal controls (C group). Blood samples were collected before and after the therapy. Serum levels of IL-6 were measured by ELISA. The phosphorylation of STAT3 protein (pSTAT3) and the percentage of Th17 cells of the CD4 T cells were analyzed by flow cytometry. The STAT3 mRNA expression was examined by Real-time PCR. The level of IL-6 in the R group was higher than that in the C group (Pâ=â0.02) whereas no difference was found between groups of N and C. The basal level of pSTAT3 in the R group was significantly higher when compared with N group (Pâ=â0.002). The percentage of Th17 cells of the CD4 T cells in the ITP patients was numerically higher than that in the controls (Pâ=â0.03). Our results indicate that ITP patient with higher basal level of pSTAT3 might have more favorite response to the corticosteroid therapy, which warrants further investigation on the prognostic role of pSTAT3 in ITP.
Assuntos
Linfócitos T CD4-Positivos/metabolismo , Púrpura Trombocitopênica Idiopática/genética , Fator de Transcrição STAT3/genética , Adulto , Idoso , Linfócitos T CD4-Positivos/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fosforilação , Púrpura Trombocitopênica Idiopática/patologia , Transdução de SinaisRESUMO
BACKGROUND: B cells play a critical role in the pathogenesis of immune thrombocytopenia (ITP), and toll-like receptor (TLR) signaling is essential for the activation of autoreactive B cells. The objective of this study was to investigate the expression profile of TLR signaling molecules in circulating and splenic CD19(+) B cells isolated from ITP patients. METHODS: CD19(+) B cells were magnetically isolated from peripheral blood and splenocytes. Human Toll-Like Receptor Signaling Pathway RT(2) Profiler™ PCR Array was used to determine the differences in mRNA expression of 84 TLR signaling pathway genes between ITP patients and controls. Flow cytometry was used to investigate intracellular expression of cytokines (IL-1ß and IL-10). RESULTS: A total of 31 genes involving TLR signaling pathways were differentially transcribed in circulating CD19(+) B cells, among which 27 were up-regulated in ITP. By comparison, differentially transcribed genes amounted to 39 in splenic B cells in ITP, among which only two were down-regulated. Up to 18 TLR signaling molecules exhibited up-regulated transcriptional levels both in splenic B cells and in circulating B cells in ITP. However, Only IL-10 and IL-1ß were significantly upregulated in both the circulating and splenic B cells of patients with ITP. Intracellular staining of IL-10 and IL-1ß confirmed the results of PCR Array. CONCLUSIONS: The expression of TLRs and downstream cytokines, including IL-10 and IL-1ß, is up-regulated in circulating and splenic B cells in ITP patients, suggesting that activated TLR signaling pathways in B cells may play dual roles in the pathophysiology of primary ITP.
Assuntos
Linfócitos B/imunologia , Interleucina-10/metabolismo , Interleucina-1beta/metabolismo , Púrpura Trombocitopênica Idiopática/imunologia , Receptores Toll-Like/metabolismo , Adulto , Idoso , Antígenos CD19/metabolismo , Células Cultivadas , Feminino , Humanos , Interleucina-10/genética , Interleucina-1beta/genética , Masculino , Pessoa de Meia-Idade , Transdução de Sinais , Receptores Toll-Like/genética , Transcriptoma , Regulação para Cima , Adulto JovemRESUMO
Primary immune thrombocytopenia (ITP) is an autoimmune heterogeneous disorder. Excessive activated CD4(+) T effector cells (Teffs) and compromised regulatory T cells (Tregs) were reported in ITP patients, yet little is known about the mechanisms. Interleukin-10 (IL-10) is an important regulatory cytokine of Tregs in inflammatory condition. It has been recently highlighted that IL-10-producing Tregs contribute to the effective controls of several autoimmune diseases. Hence this study was aimed to examine the role of IL-10 produced by Tregs in newly diagnosed ITP patients. Newly diagnosed ITP patients and healthy volunteers were enrolled to assess the numbers of peripheral Th1, Th17 cells and Tregs. CD4(+)CD25(-)Teffs and CD4(+)CD25(+)Tregs were purified. CD4(+)CD25(-)Teffs, labeled with CFSE, were cultured alone or with Tregs for 5 days, and the supernatants were then collected for IL-10 concentration test. The role of IL-10 in Tregs' inhibitory function was also determined. In ITP patients, Teffs were excessively activated, while the Tregs were numerically and functionally impaired. The percentages of IL-10(+) Tregs in Tregs' population were found elevated dramatically in ITP patients but decreased in the remitted patients. The IL-10 concentrations in the cultured supernatant were decreased in ITP patients but elevated in the remitted patients. Furthermore, the IL-10 secretion by Tregs was dramatically decreased in ITP patients. IL-10 treatment enhanced the suppression effect of Tregs toward Teffs, whereas anti-IL-10 treatment boosted the proliferation of Teffs and Th17 cells. Excessive activated Teffs and impaired Tregs play major roles in the exuberant CD4(+) T cells immune responses of ITP. The inhibitory effect of Tregs toward Teffs is largely exerted by IL-10. Insufficient secretion of IL-10 compromises the inhibitory capability of Tregs against Teffs in newly diagnosed ITP patients.
Assuntos
Interleucina-10/metabolismo , Púrpura Trombocitopênica Idiopática/imunologia , Subpopulações de Linfócitos T/imunologia , Linfócitos T Reguladores/imunologia , Adulto , Idoso , Autoimunidade , Células Cultivadas , Feminino , Humanos , Terapia de Imunossupressão , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
This study mainly focused on the impact of Hepatitis B virus (HBV) infection on the prognosis of diffuse large B cell lymphoma (DLBCL) patients in rituximab era, using a Cox regression model to ascertain the prediction value of the serum HBV marker in survivals. Three hundred and eighty four DLBCL patients treated with rituximab, cyclophosphamide, doxorubicin/epirubicin, vincristine and prednisone (R-CHOP-like regimens) or CHOP-like regimens were included. Progression-free survival (PFS) and overall survival (OS) of the patients have or have not received rituximab were analyzed separately. In the CHOP group, HBV infection has not been found a profound impact on the survivals. In the R-CHOP group, PFS and OS were inferior in HBsAg-positive patients (p=0.031 and p=0.006, respectively); after adjusting for International Prognostic Index parameters, HBsAg is an independent unfavorable factor for both PFS (RR=2.492) and OS (RR=2.589).
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígenos de Superfície da Hepatite B/metabolismo , Hepatite B/complicações , Linfoma Difuso de Grandes Células B/metabolismo , Anticorpos Monoclonais Murinos/administração & dosagem , China , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Seguimentos , Hepatite B/patologia , Hepatite B/virologia , Vírus da Hepatite B/genética , Vírus da Hepatite B/isolamento & purificação , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/virologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prednisona/administração & dosagem , Prognóstico , Estudos Retrospectivos , Rituximab , Taxa de Sobrevida , Vincristina/administração & dosagemRESUMO
This retrospective study compared efficacy and safety of fludarabine combined with intermediate-dose cytarabine (FA regimen) versus high-dose cytarabine (HiDAC regimen) as consolidation therapy in acute myeloid leukemia (AML) patients who achieved complete remission. Disease-free survival (DFS) and overall survival (OS) based on age (≥ 60, <60 years) and cytogenetics were evaluated from data between January 2005 and March 2013. Total 82 patients (FA, n = 45; HiDAC, n = 37; 14-65 years) were evaluated. Five-year DFS was 32.0% and 36.2% for FA and HiDAC groups, respectively (P = 0.729), and 5-year OS was 39.5% and 47.8% (P = 0.568), respectively. Among older patients (≥ 60 years), 3-year DFS was 26.0% for FA group and 12.5% for HiDAC group (P = 0.032), and 3-year OS was 34.6% and 12.5%, respectively (P = 0.026). In FA group, hematological toxicities were significantly lower. FA regimen was as effective as HiDAC regimen in patients with good/intermediate cytogenetics and significantly improved DFS and OS in older patients.
Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Citarabina/administração & dosagem , Leucemia Mieloide Aguda/tratamento farmacológico , Vidarabina/análogos & derivados , Adolescente , Adulto , Idoso , Antimetabólitos Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica , Quimioterapia de Consolidação , Citarabina/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Vidarabina/administração & dosagem , Vidarabina/efeitos adversos , Adulto JovemRESUMO
BACKGROUND: Regulatory B cells (Breg) are a distinct B cell subset with immunoregulatory properties. Pivotal to Breg function is interleukin-10. This study was to investigate the role of IL-10-producing B cell (B10) and its association with Treg and Th17 subsets in immune thrombocytopenia (ITP) patients. METHODS: Peripheral blood mononuclear cells from ITP patients and controls were stimulated with PMA, ionomycin, and Brefeldin A. The frequencies of CD19(+)IL-10(+) B cells, CD3(+)CD4(+)IL-17(+) Th17 cells, and CD4(+)CD25(hi)Foxp3(+) Treg cells were analyzed by flow cytometry. The mRNA expression of Foxp3 and RORγt was detected by real-time quantitative PCR. RESULTS: The number of B10 cells was elevated in ITP patients. After first-line therapies, it remained at high level in patients who achieved complete or partial response but decreased in those who acquired no response. There was a positive correlation between B10 cells and Tregs in ITP both before and after therapies. The ratio of Treg/Th17 decreased in ITP, and it strongly correlated with B10 cells. CONCLUSIONS: The frequency of B10 cells is elevated in ITP and it correlates with both the Tregs counts and the Treg/Th17 ratio. B10 cells to regulate functional T cell subsets might be impaired in patients with ITP.