RESUMO
OBJECTIVE: Graft-versus-host disease is a major complication after allogenic hematopoietic stem cell transplantation. Interferon gamma is an important pro-inflammatory cytokine involved in this disease. Cytokine gene polymorphisms are associated with functional differences in cytokine expression and can alter the clinical course of graft-versus-host disease. This study aimed to investigate the association between IFN-γ levels in saliva, blood, and IFNG polymorphisms, as well as the occurrence of acute graft-versus-host disease in allogenic HSCT. SUBJECTS AND METHODS: Fifty-eight consecutive allogenic hematopoietic stem cell transplantation recipients and their donors were prospectively studied. IFN-g levels in saliva and blood were assessed by ELISA. Samples were collected weekly from 7 days before transplantation (day -7) to 100 days after allogenic HSCT (day +100) or until death. Saliva and/or blood samples were obtained from the recipients and donors to determine IFNG gene polymorphisms. RESULTS: Increased saliva and blood IFN-g levels were observed in patients that had developed aGVHD. In the saliva, the peak levels of IFN-g could be found one week before aGVHD diagnosis, while in the blood, peak levels of IFN-g could be only observed upon diagnosis. A significant association could be identified between the recipients'IFNG genotypes and the IFN-g levels in their blood, at +14 days after HSCT. No association could be observed between IFNG gene polymorphisms and the aGVHD. CONCLUSION: The present study shows that the genetic background of recipients can influence the production of IFN-g. Moreover, as IFN-g levels in the saliva and blood were found to be associated with aGVHD development, this cytokine may be a useful predictor of acute graft-versus-host disease.
Assuntos
Doença Enxerto-Hospedeiro/imunologia , Interferon gama/análise , Polimorfismo Genético/genética , Saliva/imunologia , Proteínas e Peptídeos Salivares/análise , Doença Aguda , Adenina , Adolescente , Adulto , Idoso , Biomarcadores/análise , Criança , Pré-Escolar , Feminino , Seguimentos , Previsões , Genótipo , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Interferon gama/sangue , Interferon gama/genética , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Timina , Doadores de Tecidos , Condicionamento Pré-Transplante , Transplante Homólogo , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Glycoprotein B (gB) has been implicated in determining the pathogenicity and clinical outcomes of human cytomegalovirus (HCMV) disease. OBJECTIVE: The purpose of this study was to assess the prevalence of gB genotypes in allogeneic hematopoietic stem cell transplantation (allo-HSCT) and the relationship between it and cytokine levels in saliva and blood samples. The impact of these parameters on patients' survival was also investigated. METHODS: Samples were obtained from 63 patients receiving an allo-HSCT. HCMV gB genotyping was carried out by multiplex nested PCR. The cytokine levels were assessed using ELISA assay. RESULTS: A single or mixed genotype infection was detected in the saliva and blood of 36/63 and 52/63 subjects, respectively. Patients with gB2 in their saliva showed lower IL-10 levels in comparison with patients without gB2. Reduced blood levels of IFN-γ and IL-1ß were also found in recipients with the HCMV gB4 genotype compared with patients without it. Decreased IL-1ß and increased IL-10 blood levels were associated with lower survival. However, HCMV gB genotypes have no impact on patient outcome. CONCLUSION: Decreased IL-1ß and increased IL-10 levels in the blood are associated with lower survival. HCMV genotypes are associated with different cytokine levels in saliva and blood.
Assuntos
Citocinas/análise , Infecções por Citomegalovirus/imunologia , Citomegalovirus/genética , Transplante de Células-Tronco Hematopoéticas , Proteínas do Envelope Viral/genética , Adolescente , Adulto , Criança , Pré-Escolar , Citocinas/sangue , Citomegalovirus/imunologia , Feminino , Seguimentos , Genótipo , Humanos , Hospedeiro Imunocomprometido , Interferon gama/análise , Interferon gama/sangue , Interleucina-10/análise , Interleucina-10/sangue , Interleucina-1beta/análise , Interleucina-1beta/sangue , Interleucina-6/análise , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/virologia , Saliva/química , Saliva/imunologia , Taxa de Sobrevida , Condicionamento Pré-Transplante , Transplante Homólogo , Fator de Necrose Tumoral alfa/análise , Proteínas do Envelope Viral/imunologia , Adulto JovemRESUMO
OBJECTIVE: The purpose of this study was to investigate the use of saliva for the identification of human cytomegalovirus (HCMV) in allogeneic hematopoietic stem cell transplant patients by real time PCR compared with blood. MATERIALS AND METHODS: Saliva and blood samples were sampled weekly in 30 allogeneic hematopoietic stem cell transplant patients until 100 days after transplant. Total genomic DNA, extracted from saliva and whole-blood samples, was used for HCMV real time PCR. Nonparametric tests were performed, and P value Assuntos
Citomegalovirus/isolamento & purificação
, DNA Viral/análise
, Transplante de Células-Tronco Hematopoéticas
, Saliva/virologia
, Adolescente
, Adulto
, Antígenos Virais/análise
, Antígenos Virais/sangue
, Antivirais/uso terapêutico
, Criança
, Citomegalovirus/genética
, Citomegalovirus/imunologia
, Infecções por Citomegalovirus/diagnóstico
, Infecções por Citomegalovirus/tratamento farmacológico
, DNA Viral/sangue
, Estudos de Viabilidade
, Feminino
, Seguimentos
, Ganciclovir/uso terapêutico
, Humanos
, Estudos Longitudinais
, Masculino
, Pessoa de Meia-Idade
, Fosfoproteínas/análise
, Fosfoproteínas/sangue
, Reação em Cadeia da Polimerase
, Estudos Prospectivos
, Transplante Homólogo
, Carga Viral
, Proteínas da Matriz Viral/análise
, Proteínas da Matriz Viral/sangue
, Viremia/virologia
, Ativação Viral
, Adulto Jovem