[A prospective study of neurodevelopment of uninfected children born to human immunodeficiency virus type 1 positive mothers]. / Estudio prospectivo comparativo sobre el desarrollo psicomotor de niños, nacidos de madres positivas para el virus de inmunodeficiencia humana tipo 1 no infectados.

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.

Estudio prospectivo comparativo sobre el desarrollo psicomotor de niños, nacidos de madres positivas para el virus de inmunodeficiencia humana tipo 1 no infectados / A prospective study of neurodevelopment of uninfected children born to human inmunodeficiency virus type 1 positive mothers

Introducción. El virus de inmunodeficiencia humana tipo 1 (VIH-1) tiene tropismo por células del sistema inmune y del sistema nervioso central (SNC). La exposición intrauterina al VIH-1 causa alteraciones inmunológicas, con independencia de que el recién nacido adquiera la infección, que pueden afectar al desarrollo del SNC; además, la exposición a los antirretrovirales puede también afectar al desarrollo psicomotor. Objetivo. Evaluar el desarrollo psicomotor en niños nacidos de madres VIH-1 positivas (expuestos), y compararlos con niños sin el antecedente de la exposición al VIH-1. Sujetos y métodos. Se realizó un estudio prospectivo observacional acerca del desarrollo psicomotor de 23 niños expuestos y 20 niños no expuestos, empleando la escala de Bayley-II, el test de Denver-II y un examen neurológico, durante los primeros dos años de vida. Resultados. Los niños expuestos continuaron sin presentar la infección. Al mes de edad, los niños expuestos tuvieron valores de perímetro cefálico normales, pero menores, que los niños no expuestos. No se detectaron diferencias en el índice de desarrollo psicomotor, y el índice de desarrollo mental, sólo en el sexto mes, fue significativamente menor en los niños con exposición al VIH-1. El grupo de niños expuestos presentó más alteraciones en el test de Denver-II y en el examen neurológico, aunque sin alcanzar diferencias significativas. Conclusiones. Los resultados indican que la exposición intrauterina al VIH-1 y a los antirretrovirales de los niños que no adquieren la infección no causa alteraciones del desarrollo psicomotor al menos durante los primeros dos años de vida (AU)

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 (AU)

Toll-like receptor 4 Asp299Gly polymorphism and rheumatoid arthritis: a replicative study in three different populations

Los polimorfismos de los receptores tipo toll (TLRs) han sidoextensamente estudiados con respecto a la predisposición genéticaa varias enfermedades complejas humanas. En este contexto,el papel del polimorfismo Asp299Gly de TLR4 en la patogénesisde la artritis reumatoide (AR) no está claro. El objetivo del presenteestudio fue comprobar la posible implicación de este polimorfismoen la susceptibilidad a la AR. Genotipamos el polimorfismomediante reacción en cadena de la polimerasa y posterioranálisis de la longitud de fragmentos generados por endonucleasade restricción específica (PCR-RFLP) en tres poblacionesdiferentes de Granada (sur de España), Lugo (norte de España)y Colombia. No encontramos diferencias estadísticamente significativasen la distribución de alelos y genotipos en ninguna delas cohortes a estudio. Nuestros datos, junto a los de otros gruposde investigación, no apoyan un papel relevante del polimorfismoAsp299Gly de TLR4 en la susceptibilidad a la AR

Toll-like receptors (TLRs) polymorphisms have been extensivelystudied with regard to genetic predisposition to severalhuman complex diseases. In this context, the role of TLR4Asp299Gly in the pathogenesis of rheumatoid arthritis (RA) is notclear. The aim of this study was to test the possible implication ofthis polymorphism in the susceptibility to RA. We genotyped bypolymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) in three different populations from Granada(Southern Spain), Lugo (Northern Spain), and Colombia.We did not find statistically significant differences in the distributionof alleles and genotypes in any of the cohorts under study.Our data, together with those from other groups, do not supporta relevant role of TLR4 Asp299Gly polymorphism in the susceptibilityto RA

Toll-like receptor 4 Asp299Gly polymorphism andrheumatoid arthritis: a replicative study in three different populations

Los polimorfismos de los receptores tipo toll (TLRs) han sido extensamente estudiados con respecto a la predisposición genéticaa varias enfermedades complejas humanas. En este contexto,el papel del polimorfismo Asp299Gly de TLR4 en la patogénesis de la artritis reumatoide (AR) no está claro. El objetivo del presente estudio fue comprobar la posible implicación de este polimorfismo en la susceptibilidad a la AR. Genotipamos el polimorfismo mediante reacción en cadena de la polimerasa y posterior análisis de la longitud de fragmentos generados por endonucleasade restricción específica (PCR-RFLP) en tres poblaciones diferentes de Granada (sur de España), Lugo (norte de España)y Colombia. No encontramos diferencias estadísticamente significativas en la distribución de alelos y genotipos en ninguna de las cohortes a estudio. Nuestros datos, junto a los de otros grupos de investigación, no apoyan un papel relevante del polimorfismo Asp299Gly de TLR4 en la susceptibilidad a la AR (AU)

Toll-like receptors (TLRs) polymorphisms have been extensively studied with regard to genetic predisposition to several human complex diseases. In this context, the role of TLR4Asp299Gly in the pathogenesis of rheumatoid arthritis (RA) is not clear. The aim of this study was to test the possible implication of this polymorphism in the susceptibility to RA. We genotyped by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) in three different populations from Granada(Southern Spain), Lugo (Northern Spain), and Colombia.We did not find statistically significant differences in the distribution of alleles and genotypes in any of the cohorts under study.Our data, together with those from other groups, do not supporta relevant role of TLR4 Asp299Gly polymorphism in the susceptibilityto RA (AU)

Normal expression of IFN-gammaR in four patients with uncommon mycobacterial infection phenotypes

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.

Normal expression of IFN-gammaR in four patients with uncommon mycobacterial infection phenotypes.

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.