RESUMO
PCR of TCR/Ig gene rearrangements is considered the method of choice for minimal residual disease (MRD) quantification in BCP-ALL, but flow cytometry analysis of leukemia-associated immunophenotypes (FCM-MRD) is faster and biologically more informative. FCM-MRD performed in 18 laboratories across seven countries was used for risk stratification of 1487 patients with BCP-ALL enrolled in the NOPHO ALL2008 protocol. When no informative FCM-marker was available, risk stratification was based on real-time quantitative PCR. An informative FCM-marker was found in 96.2% and only two patients (0.14%) had non-informative FCM and non-informative PCR-markers. The overall 5-year event-free survival was 86.1% with a cumulative incidence of relapse (CIR5y) of 9.5%. FCM-MRD levels on days 15 (HzR 4.0, p < 0.0001), 29 (HzR 2.7, p < 0.0001), and 79 (HzR 3.5, p < 0.0001) associated with hazard of relapse adjusted for age, cytogenetics, and WBC. The early (day 15) response associated with CIR5y adjusted for day 29 FCM-MRD, with higher levels in adults (median 2.4 × 10-2 versus 5.2 × 10-3, p < 0.0001). Undetectable FCM- and/or PCR-MRD on day 29 identified patients with a very good outcome (CIR5y = 3.2%). For patients who did not undergo transplantation, day 79 FCM-MRD > 10-4 associated with a CIR5y = 22.1%. In conclusion, FCM-MRD performed in a multicenter setting is a clinically useful method for MRD-based treatment stratification in BCP-ALL.
Assuntos
Neoplasia Residual/tratamento farmacológico , Neoplasia Residual/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Células Precursoras de Linfócitos B/efeitos dos fármacos , Células Precursoras de Linfócitos B/patologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Citometria de Fluxo/métodos , Humanos , Imunofenotipagem/métodos , Lactente , Masculino , Pessoa de Meia-Idade , Recidiva , Adulto JovemRESUMO
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
RESUMO
The NOPHO ALL2008 is a population-based study using an unmodified pediatric protocol in patients 1-45 years of age with acute lymphoblastic leukemia. Patients with T-ALL were given a traditional pediatric scheme if fast responding (minimal residual disease (MRD) < 0.1% day 29), or intensive block-based chemotherapy if slow responding (MRD > 0.1% day 29). Both treatment arms included pediatric doses of high-dose methotrexate and asparaginase. If MRD ≥ 5% on day 29 or ≥0.1% after consolidation, patients were assigned to allogeneic hematopoietic stem cell transplantation. The 5-year overall survival of the 278 T-ALL patients was 0.75 (95% CI 0.69-0.81), being 0.82 (0.74-0.88) for patients 1.0-9.9 years, 0.76 (0.66-0.86) for those 10.0-17.9 years, and 0.65 (0.55-0.75) for the older patients. The risk of death in first remission was significantly higher in adults (12%) compared with the 1-9 years group (4%). The MRD responses in the three age groups were similar, and only a nonsignificant increase in relapse risk was found in adults. In conclusion, an unmodified pediatric protocol in patients 1-45 years is effective in all age groups. The traditional pediatric treatment schedule was safe for all patients, but the intensive block therapy led to a high toxic death rate in adults.
Assuntos
Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Pré-Escolar , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células T Precursoras/mortalidade , Resultado do Tratamento , Adulto JovemRESUMO
Minimal residual disease (MRD) measured by PCR of clonal IgH/TCR rearrangements predicts relapse in T-cell acute lymphoblastic leukemia (T-ALL) and serves as risk stratification tool. Since 10% of patients have no suitable PCR-marker, we evaluated flowcytometry (FCM)-based MRD for risk stratification. We included 274 T-ALL patients treated in the NOPHO-ALL2008 protocol. MRD was measured by six-color FCM and real-time quantitative PCR. Day 29 PCR-MRD (cut-off 10-3) was used for risk stratification. At diagnosis, 93% had an FCM-marker for MRD monitoring, 84% a PCR-marker, and 99.3% (272/274) had a marker when combining the two. Adjusted for age and WBC, the hazard ratio for relapse was 3.55 (95% CI 1.4-9.0, p = 0.008) for day 29 FCM-MRD ≥ 10-3 and 5.6 (95% CI 2.0-16, p = 0.001) for PCR-MRD ≥ 10-3 compared with MRD < 10-3. Patients stratified to intermediate-risk therapy on day 29 with MRD 10-4-<10-3 had a 5-year event-free survival similar to intermediate-risk patients with MRD < 10-4 or undetectable, regardless of method for monitoring. Patients with day 15 FCM-MRD < 10-4 had a cumulative incidence of relapse of 2.3% (95% CI 0-6.8, n = 59). Thus, FCM-MRD allows early identification of patients eligible for reduced intensity therapy, but this needs further studies. In conclusion, FCM-MRD provides reliable risk prediction for T-ALL and can be used for stratification when no PCR-marker is available.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Citometria de Fluxo/métodos , Recidiva Local de Neoplasia/patologia , Neoplasia Residual/diagnóstico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Medição de Risco/métodos , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Prognóstico , Taxa de Sobrevida , Adulto JovemRESUMO
Military conscripts are susceptible to respiratory and gastrointestinal tract infections. In previous studies probiotics have shown potency to reduce upper respiratory and gastrointestinal infections. The aim was to study whether probiotic intervention has an impact on seasonal occurrence of upper respiratory and gastrointestinal infections in two different conscript groups. In a randomised, double-blinded, placebo controlled study (https://clinicaltrials.gov NCT01651195), a total of 983 healthy adults were enrolled from two intakes of conscripts. Conscripts were randomised to receive either a probiotic combination of Lactobacillus rhamnosus GG (LGG) and Bifidobacterium animalis ssp. lactis BB12 (BB12) or a control chewing tablet twice daily for 150 days (recruits) or for 90 days (reserve officer candidates). Clinical examinations were carried out and daily symptom diaries were collected. Outcome measures were the number of days with respiratory and gastrointestinal symptoms and symptom incidence, number and duration of infection episodes, number of antibiotic treatments received and number of days out of service because of the infection. Statistically no significant differences were found between the intervention groups either in the risk of symptom incidence or duration. However, probiotic intervention was associated with reduction of specific respiratory infection symptoms in military recruits, but not in reserve officer candidates. Probiotics did not significantly reduce overall respiratory and gastrointestinal infection morbidity.
Assuntos
Bifidobacterium animalis , Gastroenteropatias/terapia , Lacticaseibacillus rhamnosus , Militares , Probióticos/uso terapêutico , Infecções Respiratórias/terapia , Adolescente , Adulto , Asma/terapia , Método Duplo-Cego , Finlândia , Humanos , Masculino , Adulto JovemRESUMO
In this paper we investigate suitability of arrays of gold coated pyramids for surface-enhanced Raman scattering (SERS) sensing applications. Pyramidarrays composed of 1000 nm pit size with 1250 nm pitch lengthwerereplicated on a plastic substrate by roll-to-roll (R2R) ultraviolet (UV) embossing. The level of SERS enhancement, and qualitative performance provided by the new substrate is investigated by comparing Raman spectrum of benzenethiol (BTh) test molecules to the benchmark Klarite SERS substrate which comprises inverted pyramid arrays(1500 nm pit size with 2000 nm pitch length) fabricated on a silicon substrate. The new substrate is found to provide upto 11 times increase in signal in comparison to the inverted pyramid (IV-pyramid) arrays fabricated on an identical plastic substrate. Numerical simulation and experimental evidence suggest that strongly confined electromagnetic fields close to the base of the pyramids, are mainly responsible for the Raman enhancement factor, instead of the fields localized around the tip. Unusually strong plasmon fields are projected upto 200nm from the sidewalls at the base of the pyramid increasing the cross sectional sensing volume.
RESUMO
Multiparameter flow cytometry (MFC) and allele-specific oligonucleotide real-time quantitative PCR (ASO RQ-PCR) are the two most sensitive methods to detect minimal residual disease (MRD) in multiple myeloma (MM). We compared these methods in 129 paired post-therapy samples from 22 unselected, consecutive MM patients in complete/near complete remission. Appropriate immunophenotypic and ASO RQ-PCR-MRD targets could be detected and MRD analyses constructed for all patients. The high PCR coverage could be achieved by gradual widening of the primer sets used for clonality detection. In addition, for 13 (55%) of the patients, reverse orientation of the ASO primer and individual design of the TaqMan probe improved the sensitivity and specificity of ASO RQ-PCR analysis. A significant nonlinear correlation prevailed between MFC-MRD and PCR-MRD when both were positive. Discordance between the methods was found in 32 (35%) paired samples, which were negative by MFC-MRD, but positive by ASO RQ-PCR. The findings suggest that with the described technique, ASO RQ-PCR can be constructed for all patients with MM. ASO RQ-PCR is slightly more sensitive in MRD detection than 6-10-color flow cytometry. Owing to technical demands ASO RQ-PCR could be reserved for patients in immunophenotypic remission, especially in efficacy comparisons between different drugs and treatment modalities.
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Citometria de Fluxo/métodos , Mieloma Múltiplo/sangue , Reação em Cadeia da Polimerase em Tempo Real/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Neoplasia ResidualRESUMO
The 'Klarite™' SERS sensor platform consisting of an array of gold coated inverted square pyramids patterned onto a silicon substrate has become the industry standard over the last decade, providing highly reproducible SERS signals. In this paper, we report successful transfer from silicon to plastic base platform of an optimized SERS substrate design which provides 8 times improvement in sensitivity for a Benzenethiol test molecule compared to standard production Klarite. Transfer is achieved using roll-to-roll and sheet-level nanoimprint fabrication techniques. The new generation plastic SERS sensors provide the added benefit of cheap low cost mass-manufacture, and easy disposal. The plastic replicated SERS sensors are shown to provide ~10(7) enhancement factor with good reproducibility (5%).
Assuntos
Equipamentos Descartáveis , Fenóis/análise , Plásticos/química , Compostos de Sulfidrila/análise , Ressonância de Plasmônio de Superfície/instrumentação , Transdutores , Desenho Assistido por Computador , Desenho de Equipamento , Análise de Falha de EquipamentoRESUMO
Immaturity of the immune system renders newborns susceptible to infections. We searched for aberrations in leucocyte signalling profiles, using phospho-specific whole-blood flow cytometry, in cord blood of nine preterm (two born before 32nd gestational week) and nine full-term infants, born by caesarean section. Thirteen adults served as reference subjects. Monocyte NF-κB phosphorylation following tumour necrosis factor (TNF) or bacterial stimulation was higher in preterm neonates than in full-term neonates or adults, p38 phosphorylation following bacterial stimulation was higher in both preterm and full-term neonates than in adults, while STAT1 phosphorylation by IFN-γ or IL-6, STAT3 phosphorylation by IL-6 and STAT5 phosphorylation by GM-CSF were lower in both full-term and preterm neonates than in adults. Neutrophil STAT1 and STAT3 phosphorylation following IFN-γ stimulation and STAT5 phosphorylation following GM-CSF stimulation were lower in newborn neonates than in adults. In both CD3(+) CD4(+) and CD3(+) CD8(+) lymphocytes, NF-κB phosphorylation by TNF was higher and STAT5 phosphorylation by IL-2 was lower in preterm and full-term newborns than in adults. STAT6 phosphorylation by IL-4 was comparable in monocytes and lymphocytes of newborns and adults. The results suggest that innate immune signalling pathways responding to inflammatory stimuli are strongly functional in leucocytes of preterm neonates, which may render these neonates susceptible to inappropriate tissue injury. In leucocytes of both preterm and full-term newborns, responses needed against intracellular pathogens, and regulatory functions show immaturities, possibly contributing to worse control of infections.
Assuntos
Linfócitos/imunologia , Monócitos/imunologia , Neutrófilos/imunologia , Transdução de Sinais/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Feminino , Sangue Fetal/metabolismo , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Humanos , Recém-Nascido/sangue , Recém-Nascido Prematuro/sangue , Interferon gama/metabolismo , Interleucina-6/metabolismo , Linfócitos/metabolismo , Masculino , Monócitos/metabolismo , NF-kappa B/metabolismo , Neutrófilos/metabolismo , Fosforilação , Fator de Transcrição STAT1/metabolismo , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT5/metabolismo , Fatores de Necrose Tumoral/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
OBJECTIVES: Reactive arthritis (ReA) is a sterile joint inflammation triggered by a remote infection and associated with human leucocyte antigen (HLA)-B27. Its pathogenesis is unknown, but abnormal response to microbial structures or endogenous inflammatory mediators may be involved. We studied responses in leucocyte signalling profiles in patients with previous ReA after a full recovery. METHOD: The study comprised 10 HLA-B27-positive healthy subjects with a history of Yersinia enterocolitica-triggered ReA (B27+ReA+) and 20 healthy reference subjects, of whom 10 carried HLA-B27 (B27+ReA-) and 10 did not (B27-ReA-). Phosphospecific fluorescent monoclonal antibodies and flow cytometry were used to determine activation of nuclear factor kappa B (NF-κB), signal transducers and activators of transcription (STATs) 1, 3, 5, and 6, and two mitogen-activated protein (MAP) kinases, p38 and extracellular signal-regulated kinase (ERK)1/2, in monocytes, lymphocytes, lymphocyte subsets, and neutrophils. B27+ReA+ and B27-ReA- whole-blood samples were incubated with Yersinia with or without infliximab to study the role of tumour necrosis factor (TNF) in lymphocyte subset activation. Samples of the three subject groups were studied using soluble bacterial or endogenous stimuli. Fluorescence levels were determined as relative fluorescence units (RFU) and the proportion of positively fluorescing cells. RESULTS: The intracellular activation of circulating leucocytes in response to soluble stimuli was consistently comparable in B27+ReA+, B27+ReA-, and B27-ReA- subjects. Infliximab inhibited Yersinia-induced lymphocyte NF-κB phosphorylation similarly in B27+ReA+ and B27-ReA- groups. CONCLUSIONS: ReA susceptibility is not reflected in leucocyte signalling profiles elicited by phlogistic stimuli. However, the possibility remains that aberrations occur in response to combinations of stimuli, such as those associated with leucocyte adhesion.
Assuntos
Artrite Reativa/imunologia , Leucócitos/imunologia , Transdução de Sinais/imunologia , Yersiniose/imunologia , Yersinia enterocolitica/imunologia , Idoso , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Antirreumáticos/farmacologia , Antirreumáticos/uso terapêutico , Artrite Reativa/tratamento farmacológico , Artrite Reativa/metabolismo , Feminino , Antígeno HLA-B27/imunologia , Antígeno HLA-B27/metabolismo , Humanos , Infliximab , Leucócitos/efeitos dos fármacos , Leucócitos/metabolismo , Masculino , Pessoa de Meia-Idade , NF-kappa B/metabolismo , Fosforilação/efeitos dos fármacos , Fosforilação/imunologia , Proibitinas , Transdução de Sinais/efeitos dos fármacos , Yersiniose/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Viral infections and graft-versus-host disease (GVHD) render an impact on both the clinical and immunological recovery following allogeneic hematopoietic stem cell transplantation (HSCT). We studied the recuperation of the immune defence after transplant in the paediatric setting and assessed the impact of early (<100 days post-HSCT) viral [cytomegalovirus (CMV), Ebstein-Barr virus (EBV) and adenovirus] reactivations/infections and GVHD. Fifty-one paediatric recipients of HSCT were enrolled. T cell recovery was evaluated on lymphocyte subpopulations using flow cytometry and functionally by measuring T cell excision circles (TRECs) and through the analysis of T lymphocyte responses to mitogens. B cell recovery was studied by flow cytometry and functionally by ELISPOT. Acute and mild chronic GVHD allowed for a brisk recovery of both cellular and humoral immunity while moderate to severe chronic graft-versus-host disease (cGVHD) associated with a significant, tampering effect on the immunological recovery after transplant. In the former group, the early viral reactivations/infections seemingly linked with a delayed recovery of T lymphocytes and low TRECs values. Moderate to severe cGVHD appears to associate with an impaired immunological recovery after HSCT. Early viral infections linked with prolonged T cell immunodeficiency and thymic dysfunction may be indicative of the presence of subclinical GVHD.
Assuntos
Linfócitos B/imunologia , Doença Enxerto-Hospedeiro/imunologia , Transplante de Células-Tronco Hematopoéticas , Linfócitos T/imunologia , Timo/imunologia , Viroses/imunologia , Adenoviridae/imunologia , Adolescente , Proliferação de Células , Criança , Pré-Escolar , Citomegalovirus/imunologia , Citometria de Fluxo , Herpesvirus Humano 4/imunologia , Humanos , Lactente , Estudos Prospectivos , Estatísticas não Paramétricas , Análise de Sobrevida , Timo/citologia , Adulto JovemRESUMO
BACKGROUND: Experimental models of hepatic ischemia/reperfusion injury have implicated a pathophysiologic role for neutrophils in subsequent hepatocellular damage. In human liver transplantation, however, the effect of reperfusion-induced neutrophil activation on initial graft function is not clear. METHODS: In 38 patients undergoing liver transplantation, neutrophil CD11b and L-selectin expression, neutrophil count, and plasma lactoferrin levels were measured. To assess changes within the graft during initial reperfusion, samples of blood entering and leaving the graft were obtained simultaneously, and transhepatic ratio calculated (hepatic vein/portal vein; 1 denotes no change, <1 a decrease, and >1 an increase across the liver). Graft steatosis, postoperative liver function, and outcome were recorded. Associations between neutrophil activation markers and outcome measures were evaluated. RESULTS: Substantial hepatic neutrophil activation occurred during initial reperfusion, demonstrated by concomitant L-selectin shedding and CD11b upregulation (transhepatic ratios 0.9 [0.7-1.0]; 1.4 [0.9-1.9]; both P < .001; portal vs hepatic vein]. Simultaneously, hepatic neutrophil sequestration and lactoferrin release occurred (0.3 [0.2-0.5]; 1.7 [1.3-3.4]; both P < .001). Neither cold ischemic time (CIT; median 5 hours 36 minutes) nor hepatic neutrophil activation during reperfusion predicted early graft function, nor was there any association between CIT and neutrophil activation. CONCLUSIONS: Despite short CIT, extensive graft neutrophil activation and sequestration occurred. This, however, was not associated with impaired early graft function, suggesting short CIT may protect against severe neutrophil-mediated injury.
Assuntos
Transplante de Fígado/fisiologia , Ativação de Neutrófilo/fisiologia , Reperfusão , Adulto , Antígenos CD/sangue , Antígeno CD11b/sangue , Feminino , Rejeição de Enxerto/epidemiologia , Sobrevivência de Enxerto/fisiologia , Veias Hepáticas/fisiologia , Humanos , Isquemia , Selectina L/metabolismo , Lactoferrina/sangue , Contagem de Leucócitos , Hepatopatias/classificação , Hepatopatias/cirurgia , Transplante de Fígado/imunologia , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Veia Porta/fisiologia , Análise de Sobrevida , Sobreviventes , Adulto JovemRESUMO
GOALS OF WORK: No blood marker available to date is useful for distinguishing infection-related from neoplasm-related fever. We evaluated the expression of the peripheral blood phagocyte CD11b/CD18 adhesion molecule complex for this purpose. MATERIALS AND METHODS: Neutrophil and monocyte CD11b/CD18 expression was assessed in two cohorts of patients with advanced solid cancer (n = 120) and in healthy controls (n = 63). The cancer series included 89 patients with verified infection, 23 without infection, and eight with neoplastic fever. CD11b/CD18 expression was measured using flow cytometry, and serum C-reactive protein (CRP) concentration was determined with immunoturbidimetric assay. RESULTS: Cancer patients with infection had higher blood neutrophil and monocyte CD11b/CD18 expression levels than patients with neoplastic fever, those with advanced cancer without infection, or healthy controls (p < 0.01 for all analyses). High CD11b/CD18 values were measured exclusively in individuals diagnosed with infection. Receiver-operating characteristic area under the curve (AUC) for neutrophil and monocyte CD11b/CD18 expression for the discrimination of infection from neoplastic fever was 0.80 (95% CI, 0.70 to 0.88), which was superior (p = 0.039 and p = 0.049, respectively) to serum CRP on admission (AUC 0.51, 0.40 to 0.62). CONCLUSIONS: Peripheral blood phagocytic cell CD11b/CD18 expression is useful for making a differential diagnosis between infection and neoplasm-related fever in cancer patients.
Assuntos
Antígeno CD11b/metabolismo , Antígenos CD18/metabolismo , Infecções/diagnóstico , Neoplasias/complicações , Adulto , Idoso , Estudos de Casos e Controles , Adesão Celular , Feminino , Citometria de Fluxo , Humanos , Infecções/complicações , Masculino , Pessoa de Meia-Idade , Monócitos/metabolismo , Neutrófilos/metabolismo , Valor Preditivo dos Testes , Curva ROC , Regulação para CimaRESUMO
We explored whether episodes stimulating leucocytes in vivo could be tracked from whole blood samples by monitoring activation of STAT1 by flow cytometry. The method was tested in hepatitis C patients (n = 9) that were on interferon (IFN)alpha regimen. CD14+ monocytes responded strongly to IFNalpha/gamma being sensitive indicators for recent immune activation. At 45 min after s.c. IFNalpha 91% of monocytes were phosphorylated STAT1+. The frequency of responding cells decreased to a base level within 6 h. Monocytes, however, had a long-term deficient phosphorylated STAT1 response to IFNalphain vitro that in patients on standard IFNalpha regimen lasted for 48 h. In patients on pegylated IFNalpha the phosphorylated STAT1 response was completely absent. We conclude that whole blood analysis of STAT1 activation by flow cytometry is applicable to monitor immune cells in patient material.
Assuntos
Citometria de Fluxo/métodos , Interferon-alfa/uso terapêutico , Monitorização Imunológica , Monócitos/metabolismo , Fator de Transcrição STAT1/metabolismo , Adulto , Animais , Feminino , Hepatite C/imunologia , Hepatite C/metabolismo , Hepatite C/terapia , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Monitorização Imunológica/métodos , Monócitos/imunologia , Fosforilação , Fator de Transcrição STAT1/sangueRESUMO
Color separation gratings (CSGs) are designed within the framework of the rigorous electromagnetic theory using a gradient method. The optimality of the scalar-theory-based solutions is estimated. The results of the experimental study of a CSG to separate three wavelengths are presented.
RESUMO
Delayed and/or insufficient T cell recovery post hematopoietic stem cell transplantation (HSCT) leads to an increased risk of morbidity and mortality. We evaluated thymic function and its association with T cell regeneration post HSCT and identified factors involved in the process among pediatric stem cell transplant recipients. T cell regeneration in 66 pediatric patients was prospectively followed by naive T cell phenotyping, measuring of T cell receptor excision circles (TRECs) and expression of Foxp3 by regulatory T cells for the first 18 months post HSCT. TRECs were lower pre-HSCT in children with a malignant than non-malignant primary disease or immunosuppressed controls (P=0.001). Naive T lymphocyte reconstitution and thymic recovery were slow in the recipients of allogeneic stem cell grafts post HSCT. Infections caused by herpesviruses had a prognostic impact on mortality. Children with low TRECs had a high mortality (P=0.05) and low TRECs were also associated with extensive chronic graft-versus-host disease from 6 months onwards. Low amount of Foxp3 pre-HSCT was associated with an increased mortality post HSCT (P=0.03). Our study indicates an association between impaired T cell regeneration and thymic dysfunction and the clinical post transplant complications in pediatric allogeneic stem cell transplantation.
Assuntos
Função Retardada do Enxerto , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Regeneração , Linfócitos T/citologia , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Fatores de Transcrição Forkhead/sangue , Doença Enxerto-Hospedeiro , Humanos , Terapia de Imunossupressão , Lactente , Infecções , Masculino , Prognóstico , Estudos Prospectivos , Receptores de Antígenos de Linfócitos T/genética , Taxa de Sobrevida , Linfócitos T/fisiologia , Timo/citologia , Transplante HomólogoRESUMO
OBJECTIVE: To compare systemic inflammation in reactive arthritis (ReA), rheumatoid arthritis (RA), and sepsis using novel markers of systemic inflammation, and to study whether they are helpful in distinguishing between ReA and RA. METHODS: In 28 patients with acute ReA, 16 patients with early untreated RA, and 25 patients with blood culture-positive sepsis, phagocyte CD 11b expression was measured by flow cytometry, serum procalcitonin (PCT) levels by immunoluminometric assay, and soluble E-selectin (sE-selectin) levels by enzyme-linked immunosorbent assay (ELISA). RESULTS: Neutrophil and monocyte CD11b expression and serum levels of PCT and sE-selectin were higher in patients with sepsis than patients with ReA or RA, or in healthy subjects (all p < 0.01). They were comparable in healthy subjects, ReA, and RA. CONCLUSION: Patients with acute ReA and early RA have normal CD11b expression levels on phagocytes and normal PCT and sE-selectin levels in serum. Elevated levels suggest possible sepsis.
Assuntos
Artrite Reativa/diagnóstico , Artrite Reumatoide/diagnóstico , Bacteriemia/diagnóstico , Biomarcadores/análise , Mediadores da Inflamação/análise , Doença Aguda , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Artrite Reativa/sangue , Artrite Reumatoide/sangue , Bacteriemia/sangue , Proteína C-Reativa/análise , Antígenos CD11/análise , Estudos de Coortes , Selectina E/análise , Feminino , Humanos , Inflamação/sangue , Inflamação/diagnóstico , Masculino , Pessoa de Meia-Idade , Probabilidade , Prognóstico , Proibitinas , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Estatísticas não ParamétricasRESUMO
AIMS: HLA-DR expression and plasma levels of pro- and anti-inflammatory cytokines (IL-6, IL-8 and IL-10) and their predictive value concerning survival of critically ill systemic inflammatory response syndrome (SIRS) patients with and without acute renal failure (ARF) were evaluated. MATERIAL: A total of 103 consecutive adult patients with SIRS from 2 university hospital intensive care units participated in the study. METHOD: Laboratory data for all patients were prospectively collected on the day of admission and 2 days thereafter. Patients with acute renal failure (ARF) and non-ARF patients were compared by Mann-Whitney U-test. Independent predictors of mortality were tested using forward stepwise logistic multiple regression analysis. The discriminative power of different variables was tested using receiver operating characteristic (ROC) curve analysis. RESULTS: ARF developed in 36 patients (35%). ARF patients showed significantly lower HLA-DR expression and higher plasma levels of IL-6, IL-8 and IL-10 than non-ARF patients. In ARF, moderate discriminative power in predicting survival was observed for day 2 IL-6 and IL-10 plasma levels (AUCs 0.703 and 0.749, respectively). CONCLUSIONS: We found no clinically significant discriminative power in predicting survival of ARF patients for monocyte HLA-DR expression or cytokine plasma levels. Therefore, our results do not support the use of HLA-DR expression or cytokine plasma levels for that purpose.
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Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/mortalidade , Antígenos HLA-DR/metabolismo , Interleucinas/sangue , Monócitos/metabolismo , Injúria Renal Aguda/etiologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Taxa de Sobrevida , Síndrome de Resposta Inflamatória Sistêmica/complicações , Síndrome de Resposta Inflamatória Sistêmica/metabolismo , Síndrome de Resposta Inflamatória Sistêmica/mortalidadeRESUMO
Loss of genomic material in 11q is one of the most common structural chromosome aberrations in B cell chronic lymphocytic leukemia (B-CLL). In order to characterize the deletions of 11q23 in B-CLL, we performed fluorescence in situ hybridization (FISH) with eight YAC (yeast artificial chromosome) probes on peripheral leukocytes of 30 patients. These YACs form a contig spanning 7.8 Mb at 11q23.1-q23.3. We found deletions in nine out of 30 cases (30%) and five of them had discontinuous deletions in this region. The region represented by YAC 755b11 (1.6 Mb in size) was involved in all cases with deletions, supporting the hypothesis that this region might contain a novel gene of pathogenic importance to B-CLL. A more distal region represented by YAC 785e12 (760 kb in size) was deleted frequently and specifically. Whether there is another novel gene of pathogenic importance to B-CLL and what is its potential relationship to the deletions in the region represented by YAC 755b11, are issues that require further studies.