RESUMO
The aim of the present study was to determine whether there is an association between serum free light chains (sFLC) quantification and the development of post-transplant lymphoproliferative disorder (PTLD), using serum samples from a nested case-control cohort of patients with renal transplant. Ten new cases of PTLD and 46 controls were enrolled. Additional comparison groups consisted of five human immunodeficiency virus (HIV)-infected individuals, five with untreated Hodgkin lymphoma and six normal individuals. Serum κ and λ FLC concentrations were measured by nephelometry and compared with reference ranges (normal and renal ranges). κ and/or λ were above the normal range in 90% of cases and in 65% of matched controls. There was no statistically significant difference between all groups, except for λ FLC concentrations between cases of PTLD and normal individuals (p = 0.016). The κ/λ sFLC ratios of cases and controls were within the renal range and normal range. Our results suggest that sFLC are not useful to predict PTLD development in renal transplant recipients.
Assuntos
Cadeias Leves de Imunoglobulina/sangue , Transplante de Rim , Linfoma/sangue , Linfoma/etiologia , Adulto , Estudos de Casos e Controles , Infecções por Vírus Epstein-Barr/sangue , Infecções por Vírus Epstein-Barr/complicações , Feminino , Infecções por HIV/sangue , Infecções por HIV/complicações , Doença de Hodgkin/sangue , Doença de Hodgkin/etiologia , Humanos , Cadeias kappa de Imunoglobulina/sangue , Cadeias lambda de Imunoglobulina/sangue , Testes de Função Renal , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
CONTEXT: Interleukins (ILs) 6, 10, and 13 seem to be important in the pathogenesis of Hodgkin lymphoma (HL), but there is insufficient data on the serum levels of these cytokines in patients with HL. OBJECTIVES: To evaluate serum levels of IL-6, IL-10, and IL-13 before and after HL treatment and to determine their potential association with clinical and laboratory parameters. DESIGN: Serum IL-6, IL-10, and IL-13 levels were quantified in the serum of 27 patients with HL by enzyme-linked immunosorbent assay. Results were evaluated against clinical and laboratory parameters, response to treatment, and presence of infection by the Epstein-Barr virus. As a control group, serum samples from 26 healthy blood donors were evaluated the same way. RESULTS: Pretreatment serum levels of IL-6 and IL-10 were significantly higher in patients with HL (P < .001), and a significant decrease was observed after treatment (P < .001). Serum IL-13 was undetectable in both patient and control groups. Serum IL-6 was higher in patients with abdominal involvement (P â=â .02), hepatomegaly (P â=â .03), B symptoms (P â=â .02), and anemia (P â=â .02). Serum IL-10 levels were higher in patients with hypoalbuminemia (P â=â .04). No association with EBV status was observed. Lymphocytopenia and B symptoms were accurate predictors of IL-6 serum levels before treatment, and higher pretreatment levels of IL-6 were observed in patients with treatment failure (P â=â .03). CONCLUSIONS: Serum levels of IL-6 and IL-10 were frequently elevated in patients with HL and decreased substantially after conventional chemotherapy. The association of elevated IL-6 and IL-10 levels in serum with some clinical and laboratory features suggests those ILs may be useful biomarkers for monitoring the HL disease and its response to chemotherapy.
Assuntos
Monitoramento de Medicamentos/métodos , Doença de Hodgkin/sangue , Interleucinas/sangue , Adulto , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/sangue , Progressão da Doença , Feminino , Doença de Hodgkin/tratamento farmacológico , Humanos , Interleucina-10/sangue , Interleucina-13/sangue , Interleucina-6/sangue , Masculino , Estadiamento de Neoplasias , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
More than 90% of patients with cancer, if diagnosed early, can be promptly treated; however diagnosis usually occurs after cancer cells have metastasized. Recent technological advances in mass spectrometry challenges the field of machine learning to model such high dimensional datasets for clinical diagnosis and prognosis. Here we use support vector machines recursive feature elimination to hunt for protein expression patterns in the serum mass spectra of Hodgkin's disease (HD) patients and control subjects (CS) that could aid in diagnosing-the disease. Based on eight selected features, support vector machines was able to correctly classify among all CS and HD patients based on the leave-one-out. We also correctly classified an independent dataset, acquired from the same samples, with the previously generated SVM model.
Assuntos
Proteínas Sanguíneas/análise , Doença de Hodgkin/diagnóstico , Proteômica , Espectrometria de Massas por Ionização por Electrospray/métodos , Doença de Hodgkin/sangue , Humanos , Reprodutibilidade dos TestesRESUMO
CONTEXT AND OBJECTIVE: Free circulating Epstein-Barr virus (EBV) DNA is often present in the plasma of Hodgkins disease patients. The aim here was to evaluate the prevalence of this finding, its correlation with the immunohistochemical expression of LMP-1 (latent membrane protein 1) and the influence of other clinical factors. DESIGN AND SETTING: Prospective study in two public tertiary institutions: Hematology Service, Universidade Federal do Rio de Janeiro, and Oncology Service, Instituto Nacional do Câncer, Rio de Janeiro. METHODS: A cohort of 30 patients with newly diagnosed Hodgkins disease was studied. The control group consisted of 13 healthy adult volunteers. EBV DNA was determined by conventional polymerase chain reaction (PCR). RESULTS: The median age was 28 years, and 16 patients were women. Advanced disease was present in 19 patients, and six were HIV-positive. EBV DNA was present in the plasma of 13 patients and one control (43% versus 8%, p = 0.03). EBV DNA prevalence was higher in HIV-positive patients (100% versus 29%, p = 0.0007) and those with advanced disease (63% versus 9%, p = 0.006). Among HIV-negative patients alone, EBV DNA prevalence remained higher in those with advanced disease. EBV DNA was found in 10/11 patients with LMP-1 expression in the lymph nodes, and in 3/19 without LMP-1 expression (kappa coefficient = 0.72). CONCLUSION: EBV DNA was present in 91% of patients with EBV-associated Hodgkins disease, and in all patients with HIV-associated Hodgkins disease. EBV DNA prevalence was higher in patients with advanced disease, irrespective of HIV status.
Assuntos
DNA Viral/sangue , Infecções por Vírus Epstein-Barr/virologia , Herpesvirus Humano 4/genética , Doença de Hodgkin/virologia , Adolescente , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Criança , Infecções por Vírus Epstein-Barr/sangue , Feminino , Infecções por HIV/sangue , Infecções por HIV/virologia , Doença de Hodgkin/sangue , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Estudos Prospectivos , Carga Viral , Proteínas da Matriz Viral/sangueRESUMO
CONTEXT AND OBJECTIVE: Free circulating Epstein-Barr virus (EBV) DNA is often present in the plasma of HodgkinÆs disease patients. The aim here was to evaluate the prevalence of this finding, its correlation with the immunohistochemical expression of LMP-1 (latent membrane protein 1) and the influence of other clinical factors. DESIGN AND SETTING: Prospective study in two public tertiary institutions: Hematology Service, Universidade Federal do Rio de Janeiro, and Oncology Service, Instituto Nacional do Câncer, Rio de Janeiro. METHODS: A cohort of 30 patients with newly diagnosed HodgkinÆs disease was studied. The control group consisted of 13 healthy adult volunteers. EBV DNA was determined by conventional polymerase chain reaction (PCR). RESULTS: The median age was 28 years, and 16 patients were women. Advanced disease was present in 19 patients, and six were HIV-positive. EBV DNA was present in the plasma of 13 patients and one control (43 percent versus 8 percent, p = 0.03). EBV DNA prevalence was higher in HIV-positive patients (100 percent versus 29 percent, p = 0.0007) and those with advanced disease (63 percent versus 9 percent, p = 0.006). Among HIV-negative patients alone, EBV DNA prevalence remained higher in those with advanced disease. EBV DNA was found in 10/11 patients with LMP-1 expression in the lymph nodes, and in 3/19 without LMP-1 expression (kappa coefficient = 0.72). CONCLUSION: EBV DNA was present in 91 percent of patients with EBV-associated HodgkinÆs disease, and in all patients with HIV-associated HodgkinÆs disease. EBV DNA prevalence was higher in patients with advanced disease, irrespective of HIV status.
CONTEXTO E OBJETIVO: O DNA do vírus Epstein-Barr (EBV) está freqüentemente presente no sangue periférico de pacientes com doença de Hodgkin. O objetivo deste estudo foi avaliar a prevalência deste achado, e correlacioná-lo com a expressão imunoistoquímica da LMP-1 (latent membrane protein 1) e a presença de outros fatores clínicos. TIPO DE ESTUDO E LOCAL: Estudo prospectivo realizado no Serviço de Hematologia da Universidade Federal do Rio de Janeiro e no Serviço de Oncologia do Instituto Nacional do Câncer, Rio de Janeiro, Brasil. MÉTODOS: Trinta pacientes com doença de Hodgkin recém-diagnosticada foram estudados, assim como um grupo controle composto por 13 indivíduos saudáveis. O DNA do EBV no plasma foi determinado pela reação em cadeia da polimerase (PCR) convencional. RESULTADOS: A idade mediana foi 28 anos e 16 pacientes eram do sexo feminino. A doença disseminada esteve presente em 19 pacientes e seis eram HIV+. O DNA do EBV foi detectado no plasma de 13 pacientes e um controle (43 por cento versus 8 por cento, p = 0,03). A prevalência do DNA do EBV foi maior nos pacientes HIV+ (100 por cento versus 29 por cento, p = 0,0007) e naqueles com doença disseminada (63 por cento versus 9 por cento, p = 0,006). Quando somente os pacientes HIV-negativos foram analisados, a prevalência do DNA do EBV permaneceu maior nos pacientes com doença disseminada. A prevalência do DNA do EBV variou de acordo com o subtipo histológico: foi de 32 por cento nos pacientes com esclerose nodular e de 100 por cento nos pacientes com celularidade mista e depleção linfocítica (p = 0,02). O DNA do EBV foi encontrado em 10/11 pacientes com a expressão da LMP-1 em linfonodos, e em 3/19 pacientes sem a expressão da LMP-1 (coeficiente de kappa = 0,72). CONCLUSÕES: O DNA circulante do EBV foi detectado no plasma de 91 por cento dos pacientes com doença de Hodgkin associada ao EBV, e em todos os pacientes com doença de Hodgkin associada ao HIV. A prevalência do DNA circulante do EBV foi detectado no plasma de 91% dos pacientes com doença de Hodgkin associada ao EBV, e em todos os pacientes com doença de Hodgkin associada ao HIV. A prevalência do DNA circulante do EBV foi maior nos pacientes com doença avançada, independentemente do status para o HIV.
Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Adulto , Pessoa de Meia-Idade , DNA Viral/sangue , Infecções por Vírus Epstein-Barr/virologia , /isolamento & purificação , Doença de Hodgkin/virologia , Biomarcadores/sangue , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Infecções por Vírus Epstein-Barr/sangue , Infecções por HIV/sangue , Infecções por HIV/virologia , Doença de Hodgkin/sangue , Imuno-Histoquímica , Reação em Cadeia da Polimerase , Estudos Prospectivos , Carga Viral , Proteínas da Matriz Viral/sangueRESUMO
MOTIVAÇAO: Neste trabalho foi analisado o perfil de proteínas séricas de pacientes com doença de Hodgkin (DH) localizada e avançada em busca de novos e potenciais biomarcadores para o diagnóstico médico. MATERIAIS E MÉTODOS: O perfil de proteínas presentes no soro de 14 indivíduos saudáveis, 14 pacientes com DH avançada e 15 pacientes com DH localizada, assim como pools de soro dos respectivos grupos, foi analisado em gel desnaturante de poliacrilamida a 12 por cento corado pela prata. A densitometria e a intensidade média das bandas de interesse foram estudadas utilizando-se o Kodak 1D Scientific Imaging System. RESULTADOS E CONCLUSÕES: O perfil protéico apresentou acentuada variação entre os pacientes examinados; entretanto foi observada a indução predominante de determinadas proteínas (aproximadamente 26kDa e 18kDa), cuja expressão foi substancialmente diferente quando em comparação com os controles (p < 0,01). Estas proteínas podem potencialmente constituir-se em marcadores moleculares de acompanhamento da evolução e do tratamento da doença.
Assuntos
Humanos , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/sangue , Eletroforese em Gel de Poliacrilamida , Biomarcadores Tumorais/análiseRESUMO
OBJECTIVE: Inhibin B produced by Sertoli cells may be an important marker of seminiferous tubule function in patients treated with chemotherapy (CT). The aim of this study was to evaluate the inhibin B/FSH ratio to detect male gonadal dysfunction in cancer survivors treated in childhood and adolescence. PATIENTS: Twenty-one male patients (group A) treated with 6-10 courses of CT for Hodgkin's disease during childhood and adolescence were examined 3-11 years after the conclusion of treatment. Twenty healthy young men (18-23 years old) were used as controls (group B). METHODS: Serum samples for the determination of inhibin B, follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), sex hormone-binding globulin (SHBG) and semen for analysis were collected. RESULTS: The median testicular volume of patients of group A was lower than those of group B (p = 0.001) and a positive correlation was found between testicular size and sperm count (r = -0.5, p = 0.01). Semen analysis revealed azoospermia in 11 patients, severe oligospermia in four and normal sperm count in three. No significant difference was found in the median of T, LH, SHBG, inhibin B concentrations and T/LH ratio between the groups. Serum inhibin B was correlated with the serum FSH levels (r = -0.5, p = 0.02). Median FSH was significantly higher (p = 0.0001), and median inhibin B/FSH ratio was significantly lower in group A than in controls (p = 0.0002), but the inhibin B/FSH ratio was higher in the patients with normal sperm count than in those with oligospermia (p = 0.00004). CONCLUSIONS: These results show that the cytotoxic effects of CT cause severe damage to the germinal epithelium with subtle effects on Sertoli cells. To assess Sertoli cell function in men with primary testicular damage after treatment with CT in childhood and adolescence, the inhibin B level needs to be interpreted in the context of the circulating FSH, especially when normal FSH levels are observed.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/uso terapêutico , Hormônio Foliculoestimulante/sangue , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/fisiopatologia , Inibinas/sangue , Prednisona/uso terapêutico , Procarbazina/uso terapêutico , Células de Sertoli/efeitos dos fármacos , Testículo/fisiopatologia , Vincristina/uso terapêutico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores/sangue , Estudos de Casos e Controles , Criança , Pré-Escolar , Ciclofosfamida/efeitos adversos , Doença de Hodgkin/sangue , Doença de Hodgkin/patologia , Humanos , Masculino , Oligospermia/etiologia , Tamanho do Órgão/efeitos dos fármacos , Prednisona/efeitos adversos , Procarbazina/efeitos adversos , Contagem de Espermatozoides , Análise de Sobrevida , Testículo/patologia , Vincristina/efeitos adversosRESUMO
We report an unusual case of modular sclerosing Hodgkin's disease in a 17 year old women presenting with intermittent fever, progressive weight loss and enlarged cervical and anxillary lymp nodes. Laboratory test revealed severe Coombs' positive haemolytic anaemia, and progressive thrombocytopenia and leucopenia, associated with erythroid, myeloid and megakaryocytic hyperplasia, but with no evidence of lymphomatous infiltration in the bone marrow. Transfusion of compatible blood became possible only after prednisone therapy and a single intravenous dose of vincristine. Appropriate chemotherapy led to normalization of the peripheral blood counts and a negative direct Coombs' test.(AU)
Assuntos
Adolescente , Relatos de Casos , Feminino , Humanos , Trombocitopenia/complicações , Anemia Hemolítica Autoimune , Doença de Hodgkin/complicações , Doença de Hodgkin/sangue , Transfusão de SangueRESUMO
We report an unusual case of modular sclerosing Hodgkin's disease in a 17 year old women presenting with intermittent fever, progressive weight loss and enlarged cervical and anxillary lymp nodes. Laboratory test revealed severe Coombs' positive haemolytic anaemia, and progressive thrombocytopenia and leucopenia, associated with erythroid, myeloid and megakaryocytic hyperplasia, but with no evidence of lymphomatous infiltration in the bone marrow. Transfusion of compatible blood became possible only after prednisone therapy and a single intravenous dose of vincristine. Appropriate chemotherapy led to normalization of the peripheral blood counts and a negative direct Coombs' test.