Assuntos
Adenocarcinoma de Pulmão/tratamento farmacológico , Diabetes Mellitus/induzido quimicamente , Cetoacidose Diabética/induzido quimicamente , Coma Hiperglicêmico Hiperosmolar não Cetótico/induzido quimicamente , Inibidores de Checkpoint Imunológico/efeitos adversos , Neoplasias Pulmonares/tratamento farmacológico , Nivolumabe/efeitos adversos , Dor Abdominal/fisiopatologia , Injúria Renal Aguda/fisiopatologia , Adenocarcinoma de Pulmão/secundário , Idoso , Autoanticorpos/metabolismo , Confusão/fisiopatologia , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/metabolismo , Diabetes Mellitus/fisiopatologia , Cetoacidose Diabética/tratamento farmacológico , Cetoacidose Diabética/metabolismo , Cetoacidose Diabética/fisiopatologia , Feminino , Cadeias HLA-DRB1/genética , Humanos , Coma Hiperglicêmico Hiperosmolar não Cetótico/tratamento farmacológico , Coma Hiperglicêmico Hiperosmolar não Cetótico/metabolismo , Coma Hiperglicêmico Hiperosmolar não Cetótico/fisiopatologia , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Polidipsia/fisiopatologia , Poliúria/fisiopatologiaRESUMO
Promising results of umbilical cord blood transplantation (UCBT) from unrelated donors have been reported in patients with hematologic disorders. These transplants, having potential to trigger beneficial donor-versus-recipient natural killer (NK) cell-mediated alloreaction, we have conducted the first extensive analysis of the phenotypic and functional properties of NK cells after UCBT. NK cells from 25 patients with high-risk hematologic malignancies were compared with cells derived from both healthy adult and CB cells. We found that following UCBT, NK cells display not only some phenotypic features associated with maturity but also unique characteristics that make them fully functional against leukemic blasts. We propose that this full functionality of alloreactive donor-derived NK may drive graft-versus-leukemia reactions after UCBT.
Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Efeito Enxerto vs Leucemia/imunologia , Neoplasias Hematológicas/terapia , Células Matadoras Naturais/imunologia , Adolescente , Adulto , Feminino , Hematopoese , Teste de Histocompatibilidade , Humanos , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Doadores de Tecidos , Condicionamento Pré-Transplante/métodos , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: The significance of anti-human leukocyte antigen immunoglobin G (IgG) detected in the posttransplantation course of heart graft recipients remains unclear. METHOD: Sera from 121 cardiac allograft recipients transplanted between January 1992 and December 1994 were screened for the presence of lymphocytotoxic antibodies in the first year after transplantation. Dithiothreitol was used to differentiate IgG from immunoglobulin M. RESULTS: Nineteen patients (15%) had cytotoxic IgG develop, mainly during the first month after transplantation. The percentage of women was higher in this group (42% vs 15.7%; P <.05). Donor to recipient mismatches for sex, blood typing, cytomegalovirus serology, and human leukocyte antigen typing were comparable between IgG producers and nonproducers. The frequency of acute allograft dysfunction during the first year after transplantation was significantly higher among patients producing IgG (42% vs 5.9; P <.001). Most of these acute allograft dysfunctions were independent of cellular rejection lesions but were associated with a thickening of the posterior wall and the interventricular septum during the acute episode. Finally, all the patients but one recovered. Recurrences were not uncommon and, at 1 year after transplantation, the dose of cyclosporine used in patients producing IgG was significantly greater, as was the left ventricular thickness. CONCLUSION: Posttransplantation cytotoxic IgG is not uncommon and appears to be associated with a high rate of acute allograft dysfunction. Development of these antibodies can be caused by a previous undetected immunization, as suggested by the higher percentage of women in the producer group. Correlation with histologic lesions of humoral rejection are discussed.
Assuntos
Rejeição de Enxerto/imunologia , Transplante de Coração/imunologia , Imunoglobulina G/análise , Adolescente , Adulto , Idoso , Ciclosporina/uso terapêutico , Feminino , Seguimentos , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Prognóstico , Medição de Risco , Transplante Homólogo , Função Ventricular EsquerdaRESUMO
BACKGROUND: As only a few studies have examined the prevalence of various hepatitis C virus (HCV) subtypes in blood donors, information about the variability and route of infection in apparently healthy persons is limited. STUDY DESIGN AND METHODS: Blood donations collected at a large Parisian hospital (52,441) were investigated for antibodies to HCV. Serum samples were screened with an enzyme immunoassay. All HCV-positive donations were retested with a second enzyme immunoassay and confirmed by immunoblot. The HCV genotype was determined for all polymerase chain reaction-positive subjects. Untypable genotypes were sequenced in the NS5B region. RESULTS: In total, 83 (0.26%) blood donors were anti-HCV positive. Men (0.34%) were significantly more likely to be infected (p < 0.001) than women (0.19%). Prevalence rates in men between 20 and 39 years of age were higher than those in similar women (p = 0.01), but greater in women aged from 50 to 65 years (p = 0.05). Fifty-five sera were viremic, of which 49 could be genotyped by a line probe assay. One new HCV type 1 subtype and three new HCV type 2 subtypes were discovered. In total, 28, 10, 11, 5, and 1 serum samples were grouped into HCV types 1 through 5, respectively, involving a total of 13 subtypes. The mean age of HCV type 2-infected donors was 42 +/- 11 years, but that for type 3-infected subjects was only 30 +/- 4 years (p = 0.0048). Forty-nine subjects showed elevated alanine aminotransferase levels; 39 (80%) of these subjects were viremic (p < 0.05). CONCLUSION: Among the sampled population, an HCV prevalence rate of 0.26 percent was found, with the five most common European genotypes causing the infections. Four new subtypes were discovered. Correlation between genotype and risk factors was not apparent, but links with age, sex, and ethnic origin emerged.
Assuntos
Doadores de Sangue , Hepacivirus/genética , Adulto , Idoso , Feminino , Genótipo , Hepacivirus/classificação , Hepatite C/epidemiologia , Hepatite C/virologia , Anticorpos Anti-Hepatite C/sangue , Humanos , Immunoblotting , Masculino , Pessoa de Meia-Idade , Paris/epidemiologia , Reação em Cadeia da Polimerase , RNA Viral/análise , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
The prevalence of hepatitis C virus (HCV) antibodies, HCV infection, and genotypes was studied in a rural population of the Central African Republic. In five villages, blood samples were taken from all the inhabitants present during the survey, belonging to Pygmies (299) and to Bantu and Banda ethnic groups (247). Using a second-generation ELISA screening and confirmation by immunoblot assay for the detection of HCV antibodies, all the Pygmies were negative, whereas seven Bantus/Bandas, aged > 35 years and with no familial relationship, were positive, giving a prevalence of 2.8% in this ethnic group. Five samples were also PCR positive; all belonged to genotype 4, but with three new subtypes identified by phylogenic analysis. These results indicate the co-existence of different HCV subtypes and raise questions about the natural transmission of HCV in this secluded population.