RESUMO
INTRODUCTION: The human immunodeficiency virus type 1 (HIV-1) has tropism for the immune and central nervous systems (CNS). Intrauterine exposure to HIV-1 induces immunological alterations, independent of infection that might affect the development of the CNS. Similarly, the intrauterine exposure to antiretrovirals might also affect the neurodevelopment. AIM: To evaluate the neurodevelopment of babies born to HIV-1 positive mothers (exposed) and compare with babies born to HIV-1 negative mothers (unexposed). SUBJECTS AND METHODS: We carried-out an observational prospective study of neurodevelopment of 23 exposed and 20 unexposed children using the infant development scale Bayley-II, and the Denver-II test, neurological examination and anthropometric measurements during the first two years of life. RESULTS: None of the exposed babies acquired the infection. At one month of age the exposed babies exhibit normal but statistically lower values in the head circumference, compared to unexposed neonates. No differences were found in the psychomotor development index between both studied groups and exposed babies exhibited a lower mental development index but only at six months of age. The exposed babies exhibited a higher number of alterations during the neurological and Denver-II tests without reaching significant differences. CONCLUSIONS: The results suggest that intrauterine exposure to HIV-1 and to antiretrovirals in uninfected children born to HIV-1 positive mothers does not induce alterations in the neurodevelopment, at least during the first two years of life.
Assuntos
Sistema Nervoso Central/crescimento & desenvolvimento , Sistema Nervoso Central/fisiologia , Desenvolvimento Infantil/fisiologia , Infecções por HIV/fisiopatologia , HIV-1 , Mães , Sistema Nervoso Central/virologia , Pré-Escolar , Feminino , Soropositividade para HIV , Humanos , Lactente , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Estudos ProspectivosRESUMO
Several primary immunodeficiency diseases affecting the interleukin 12/interferon gamma (IFN-gamma) pathway have been identified, most of them characterized by recurrent and protracted infections produced by intracellular microorganisms, particularly by several species of mycobacteria. In the present study we analyzed the expression of IFN-gamma receptor (IFN-gammaR) and signal transducer and activator of transcription 1 (STAT-1) in 4 children with Mycobacterium tuberculosis infection of uncommon clinical presentation. These molecules were evaluated by flow cytometry and Western blotting in B cells transformed with Epstein-Barr virus and mutations were scanned by single-strand conformational polymorphisms and DNA sequencing. The expression of IFN-gammaR1 was normal in all 4 patients. The genetic analysis of IFN-gammaR1 and IFN-gammaR2 coding sequences did not reveal any mutation. The expression of the STAT-1 molecule was similar in patients and healthy controls; however, when the phosphorylation of this transcription factor in response to IFN-gamma activation was evaluated by Western blot, a significant lower signal was evident in one patient. These data indicate that there are no alterations in the expression or function of the IFN-gammaR chains in these patients. However, the low level of STAT-1 phosphorylation found in one of these patients might be explained by a defect in one of the molecules involved in the signal transduction pathway after IFN-gamma interacts with its receptor. In the other three patients the inability to eliminate the mycobacteria may be due to a defect in another effector mechanism of the mononuclear phagocytes.
Assuntos
Humanos , Masculino , Feminino , Lactente , Criança , Infecções por Mycobacterium , Mycobacterium tuberculosis , Western Blotting , Estudos de Casos e Controles , DNA Bacteriano , Citometria de Fluxo , Genoma Bacteriano , Contagem de Linfócitos , Fenótipo , Fosforilação , Polimorfismo Conformacional de Fita Simples , TuberculoseRESUMO
Several primary immunodeficiency diseases affecting the interleukin 12/interferon gamma (IFN-gamma) pathway have been identified, most of them characterized by recurrent and protracted infections produced by intracellular microorganisms, particularly by several species of mycobacteria. In the present study we analyzed the expression of IFN-gamma receptor (IFN-gammaR) and signal transducer and activator of transcription 1 (STAT-1) in 4 children with Mycobacterium tuberculosis infection of uncommon clinical presentation. These molecules were evaluated by flow cytometry and Western blotting in B cells transformed with Epstein-Barr virus and mutations were scanned by single-strand conformational polymorphisms and DNA sequencing. The expression of IFN-gammaR1 was normal in all 4 patients. The genetic analysis of IFN-gammaR1 and IFN-gammaR2 coding sequences did not reveal any mutation. The expression of the STAT-1 molecule was similar in patients and healthy controls; however, when the phosphorylation of this transcription factor in response to IFN-gamma activation was evaluated by Western blot, a significant lower signal was evident in one patient. These data indicate that there are no alterations in the expression or function of the IFN-gammaR chains in these patients. However, the low level of STAT-1 phosphorylation found in one of these patients might be explained by a defect in one of the molecules involved in the signal transduction pathway after IFN-gamma interacts with its receptor. In the other three patients the inability to eliminate the mycobacteria may be due to a defect in another effector mechanism of the mononuclear phagocytes.