RESUMO
In order to investigate hepatitis C virus (HCV) persistence and replication in peripheral blood mononuclear cells (PBMC) from a group of haemophilic individuals, HCV production and release to PBMC culture supernatants (SNs) from HCV singly infected patients and HIV/HCV co-infected patients was studied. HCV RNA+ SNs were found more frequently from HIV/HCV co-infected individuals (89.5 %) with poor reconstitution of their immune status than from singly HCV-infected patients (57 %) or from HIV/HCV co-infected individuals with a good response to highly active anti-retroviral therapy (50 %). The presence of the HCV genome in culture SNs was associated with lower CD4+ T-cell counts and with a more severe clinical picture of HIV infection. In spite of prolonged negative HCV viraemia, PBMC from HIV/HCV co-infected patients released the HCV genome after culture. HCV permissive PBMC allowed generation of HCV productive B cell lines with continuous HCV replication. These findings add further weight to the involvement of PBMCs in persistence of HCV infection and emphasize the role of B lymphocytes as HCV reservoirs.
Assuntos
Hepacivirus/isolamento & purificação , Hepatite C Crônica/virologia , Leucócitos Mononucleares/virologia , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Linfócitos B/virologia , Contagem de Linfócito CD4 , Linhagem Celular Tumoral/virologia , Células Cultivadas , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Hepacivirus/genética , Hepatite C Crônica/complicações , Hepatite C Crônica/imunologia , Humanos , RNA Viral/análise , Fatores de TempoRESUMO
Besides intron 22 factor VIII gene inversion (Inv22), intron 1 inversion (Inv1) has recently been reported as a further recurrent mutation that causes approximately 5% of severe haemophilia A (HA) cases. We analysed the presence of the Inv1 in a group of 64 severe HA-affected families from Argentina, and found only one positive case. This Inv1 patient has not developed a factor VIII inhibitor, and the screening for small mutations in the coding sequences of the factor VIII gene did not detect any additional defect in this case. The Inv1 genotyping was further applied to analyse the haemophilia carrier status of the proband's sister. In addition, we studied the accuracy of the current polymerase chain reaction-based method to investigate the Inv1, and confirmed the absence of amplimer length polymorphisms associated to the Inv1-specific polymerase chain reaction amplifications in 101 X-chromosome haplotypes from unrelated Argentinian healthy males. In order to discuss Inv1 mutation frequency in severe HA and the risk of inhibitor formation, a review of the literature was included. Our data highlight the importance of analysis of the Inv1 in Inv22-negative severe HA cases. This will benefit both genetic counselling and the study of the relationship between genotype and inhibitor development.
Assuntos
Fator VIII/genética , Hemofilia A/genética , Íntrons/genética , Mutação , Argentina , Família , Feminino , Testes Genéticos , Hemofilia A/patologia , Humanos , Masculino , Reação em Cadeia da Polimerase , Análise de Sequência de DNARESUMO
La trombocitopenia es una anomalía usual e importante en pacientes con coinfección por HIV-1/HCV. La esplenomegalia es un hallazgo frecuente en estos pacientes y, usualmente, causa hiperesplenismo y trombocitopenia. Analizamos los resultados clínicos de un método invasivo mínimo (embolización de la arteria esplénica) para el tratamiento de la trombocitopenia secundaria al hiperesplenismo y refractaria a otras terapias en dos pacientes hemofílicos, infectados por el HIV-1 y con cirrosis causada por la infección crónica por HCV. Estos resultados sugieren que la embolización de la arteria esplénica es un método seguro, poco traumático y efectivo para el tratamiento de la esplenomegalia y el hiperesplenismo en pacientes con coinfección por HIV-1/HCV.
Assuntos
Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Embolização Terapêutica , Hemofilia A , Hiperesplenismo , Hepatite C , Infecções por HIV , HIV-1 , Hiperesplenismo , Cirrose Hepática , Esplenectomia , Artéria Esplênica , TrombocitopeniaRESUMO
La trombocitopenia es una anomalía usual e importante en pacientes con coinfección por HIV-1/HCV. La esplenomegalia es un hallazgo frecuente en estos pacientes y, usualmente, causa hiperesplenismo y trombocitopenia. Analizamos los resultados clínicos de un método invasivo mínimo (embolización de la arteria esplénica) para el tratamiento de la trombocitopenia secundaria al hiperesplenismo y refractaria a otras terapias en dos pacientes hemofílicos, infectados por el HIV-1 y con cirrosis causada por la infección crónica por HCV. Estos resultados sugieren que la embolización de la arteria esplénica es un método seguro, poco traumático y efectivo para el tratamiento de la esplenomegalia y el hiperesplenismo en pacientes con coinfección por HIV-1/HCV.(AU)