RESUMEN
Forkhead box protein 3 (FoxP3)(+) regulatory T cells (Tregs ) are important not only in regulating the development of autoimmune conditions, but also in chronic infectious diseases. Given their cardinal function in suppressing immune activation, research has focused upon whether they play a detrimental role in chronic infections, particularly HIV. While the role of Tregs in HIV has been investigated intensively, it remains an unresolved topic. However, it is generally accepted that Tregs are susceptible to HIV infection and are preferentially preserved over conventional CD4(+) T cells. It is unknown whether the peripheral-induced or the thymic-derived Tregs are more susceptible to HIV cytotoxicity. It has been recognized that Tregs can be segregated into two subsets based on Helios expression, with the vast majority being Helios(+) . This study examines the impact of HIV infection on total Tregs and their Helios subsets in a perinatal-acquired HIV-infected paediatric population. The finding indicates a selective expansion or survival of Tregs in association with CD4 depletion and increased viraemia. The Helios(+) and Helios(-) subsets within Tregs appear to be equally affected. However, the Helios(+) Tregs seem to be more preserved in patients with low CD4(+) ≤ 25% and detectable plasma HIV RNA >20 copies/ml. In this group, the frequencies of Tregs are increased, but their numbers appear insufficient to restrain immune activation. In conclusion, our findings suggest that both Helios subsets of Tregs are susceptible to HIV infection and are preferentially preserved compared to conventional CD4(+) T cells.
Asunto(s)
Factores de Transcripción Forkhead/inmunología , Regulación de la Expresión Génica/inmunología , Infecciones por VIH/inmunología , VIH-1/inmunología , Factor de Transcripción Ikaros/inmunología , Linfocitos T Reguladores/inmunología , Adolescente , Adulto , Niño , Preescolar , Enfermedad Crónica , Femenino , Factores de Transcripción Forkhead/biosíntesis , Infecciones por VIH/sangre , Infecciones por VIH/congénito , Infecciones por VIH/patología , VIH-1/metabolismo , Humanos , Factor de Transcripción Ikaros/biosíntesis , Lactante , Masculino , ARN Viral/sangre , ARN Viral/inmunología , Linfocitos T Reguladores/metabolismo , Linfocitos T Reguladores/patología , Timo/inmunología , Timo/metabolismo , Timo/patologíaRESUMEN
Pulmonary hypertension (PH) is a frequently under recognized complication of myelofibrosis (MF). The pathophysiology of PH in MF is unknown and no definitive therapies have been established. We studied 15 patients with MF-associated PH and compared their echocardiographic and PH relevant biomarkers (nitric oxide (NO), N-terminal pro-hormone of brain natriuretic peptide (NT-pro BNP), von Willebrand antigen (vWB), ristocetin-cofactor activity (RCA) and uric acid (UA)) pre- and post-ruxolitinib treatment. Ruxolitinib decreased the plasma levels of NT-pro BNP (73%; P=0.043), UA (60%), vWB (86%) and RCA (73%; P=0.036). Improvements in echocardiographic findings were also seen in 66% of patients (P=0.022). Furthermore, marked increase in NO compared with baseline (69.75 vs 40.1 picomolar (pM); P=0.001) was observed post-ruxolitinib therapy, whereas no changes were noted with conventional therapies. Treatment with ruxolitinib also resulted in the reduction of key cytokines (tumor necrosis factor alpha, interleukin-4 (IL-4), IL-6 and IL-8) and induction of interferon-gamma. Animal studies further supported the role of ruxolitinib in the induction of NO levels. In conclusion, aberrant Janus kinase (JAK)-signal transducer and activator of transcription signaling in MF may mediate PH through dysregulation of NO and cytokine levels, which can be restored by therapy with JAK inhibitors suggesting that inhibition of this pathway is a novel target for the management of patients with PH.
Asunto(s)
Hipertensión Pulmonar/tratamiento farmacológico , Hipertensión Pulmonar/etiología , Mielofibrosis Primaria/complicaciones , Pirazoles/uso terapéutico , Anciano , Anciano de 80 o más Años , Animales , Biomarcadores/sangre , Citocinas/sangre , Modelos Animales de Enfermedad , Ecocardiografía , Femenino , Ferritinas/sangre , Humanos , Hipertensión Pulmonar/diagnóstico , Quinasas Janus/antagonistas & inhibidores , Masculino , Ratones Noqueados , Persona de Mediana Edad , Óxido Nítrico/sangre , Nitrilos , Mielofibrosis Primaria/sangre , Mielofibrosis Primaria/genética , PirimidinasRESUMEN
Circulating cardiac troponins are markers of myocardial injury. We sought to determine whether cardiac troponin I (cTnI), measured by a sensitive assay, is associated with disease severity and prognosis in pulmonary arterial hypertension (PAH). cTnI was measured in 68 patients with PAH diagnostic category 1 in a research-based sensitive immunoanalyser with a lower limit of detection of 0.008 ng · mL(-1). The associations between cTnI and PAH severity and clinical outcomes were assessed using Chi-squared and Wilcoxon rank sum tests, Kaplan-Meier analysis and Cox regression models. cTnI was detected in 25% of patients. Patients with detectable cTnI had more advanced functional class symptoms, a shorter 6-min walk distance, more pericardial effusions, larger right atrial area, and higher B-type natriuretic peptide and C-reactive protein levels. 36-month transplant-free survival was 44% in patients with detectable cTnI versus 85% in those with undetectable cTnI. cTnI was associated with a 4.7-fold increased risk of death related to right ventricular failure or transplant (hazard ratio 4.74, 95% CI 1.89-11.89; p<0.001), even when adjusted individually for known parameters of PAH severity. Elevated plasma cTnI, even at subclinically detectable levels, is associated with more severe disease and worse outcomes in patients with PAH.
Asunto(s)
Hipertensión Pulmonar , Índice de Severidad de la Enfermedad , Troponina I/sangre , Adulto , Biomarcadores/sangre , Proteína C-Reactiva/metabolismo , Hipertensión Pulmonar Primaria Familiar , Femenino , Humanos , Hipertensión Pulmonar/sangre , Hipertensión Pulmonar/diagnóstico , Hipertensión Pulmonar/mortalidad , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Péptido Natriurético Encefálico/sangre , Derrame Pericárdico/sangre , Derrame Pericárdico/diagnóstico , Derrame Pericárdico/mortalidad , Valor Predictivo de las Pruebas , Pronóstico , Modelos de Riesgos Proporcionales , Factores de Riesgo , Sensibilidad y EspecificidadRESUMEN
Biomarkers are objectively measured characteristics used as indicators of disease in clinical practice and as surrogate endpoints in clinical trials. The six-minute walk test has been widely used as a trial endpoint in pulmonary arterial hypertension (PAH) to gain approval for targeted therapies. Other biomarkers have been studied to overcome certain limitations of the walk test. Potential clinical applications for biomarkers in PAH include screening, determination of prognosis, and monitoring response to therapy. Measurement of the B-type natriuretic peptides is currently recommended by guidelines, despite a lack of appropriate validation in the PAH population. Novel biomarkers based on recently discovered pathobiologic pathways have been identified, like CXC chemokine ligand 10, C-reactive protein, high-density lipoprotein cholesterol and growth-differentiation factor-15. Rigorous statistical, biologic and clinical validation should be necessary before any biomarker can be endorsed for widespread clinical use.
Asunto(s)
Hipertensión Pulmonar , Biomarcadores , Hipertensión Pulmonar Primaria Familiar , Hemodinámica/fisiología , Humanos , Hipertensión Pulmonar/diagnóstico , Hipertensión Pulmonar/fisiopatología , Pronóstico , Sensibilidad y EspecificidadRESUMEN
We report the development of Campylobacter jejuni enteritis in a patient with preexisting humoral and cellular immune recognition of C. jejuni antigens. This is one of few studies in which the immunologic status of a person with regard to C. jejuni before and after C. jejuni infection is directly compared, and it is the only study of which we are aware that includes measurements of cellular immunity. The findings may be important to Campylobacter vaccine development efforts.
Asunto(s)
Infecciones por Campylobacter/inmunología , Campylobacter jejuni , Enteritis/inmunología , Anticuerpos Antibacterianos/sangre , Antígenos Bacterianos , Infecciones por Campylobacter/etiología , Campylobacter jejuni/inmunología , Humanos , Inmunidad Celular , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Masculino , Persona de Mediana EdadRESUMEN
A preterm breast-fed infant had three episodes of type Ia/c group B streptococcus septicemia. After the second episode rifampin was given to the infant, but further Ia/c exposure to maternal breast milk ensued. We propose rifampin treatment for both the mother and infant in cases of recurrent group B streptococcus disease.
Asunto(s)
Leprostáticos/uso terapéutico , Leche Humana/microbiología , Rifampin/uso terapéutico , Infecciones Estreptocócicas/tratamiento farmacológico , Streptococcus agalactiae/aislamiento & purificación , Lactancia Materna , Electroforesis en Gel de Campo Pulsado , Femenino , Humanos , Recién Nacido , RecurrenciaAsunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/complicaciones , Neumonía por Pneumocystis/complicaciones , Infecciones Oportunistas Relacionadas con el SIDA/inmunología , Adulto , Recuento de Linfocito CD4 , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/diagnóstico , Infecciones por VIH/transmisión , Humanos , Inmunocompetencia , Lactante , Recién Nacido , Intercambio Materno-Fetal , Neumonía por Pneumocystis/inmunología , Embarazo , Complicaciones Infecciosas del EmbarazoAsunto(s)
Giardia lamblia/parasitología , Giardia lamblia/patogenicidad , Giardiasis/etiología , Animales , Antiprotozoarios/administración & dosificación , Antiprotozoarios/efectos adversos , Antiprotozoarios/uso terapéutico , Preescolar , Furazolidona/administración & dosificación , Furazolidona/efectos adversos , Furazolidona/uso terapéutico , Giardiasis/diagnóstico , Giardiasis/tratamiento farmacológico , Humanos , Metronidazol/administración & dosificación , Metronidazol/efectos adversos , Metronidazol/uso terapéutico , Quinacrina/administración & dosificación , Quinacrina/efectos adversos , Quinacrina/uso terapéuticoRESUMEN
Shigella sonnei infection resulting from oral administration of 500 colony-forming units was followed in 11 volunteers with the objective of studying the immune response and pathogenesis. Characterization of infection included recording of signs and symptoms, excretion of S. sonnei in stool, measurement of humoral tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), interferon-gamma (IFN-gamma), C-reactive protein, IL-2 receptor, soluble CD8, antibody-antigen complexes, and endotoxin. Measurements were also made of the immune response including lymphocytes secreting antibody to S. sonnei O antigen and serum antibody to this antigen. Six of the volunteers developed typical shigellosis with excretion of bacteria in stool and systemic signs and symptoms, three excreted bacteria but did not show illness, and two showed no evidence of infection or illness. Shigellosis was characterized by excretion in stool of S. sonnei beginning on average 1.3 days after ingestion. Excretion of S. sonnei (mean of time of the first positive cultures) was followed in sequence by the onset of increases in TNF-alpha (10 hr), liquid stools (14 hr), fever and dysentery (18 hr), IFN-gamma (22 hr), and C-reactive protein (34 hr). A S. sonnei-specific immune response was demonstrated somewhat later, between days 4 and 7 postinfection by antibody-secreting cells, and between days 7 and 14 postinfection by humoral antibody. Shigellosis was not associated with increased humoral IL-1 beta, endotoxin, or antigen-antibody complexes.
Asunto(s)
Proteínas de Fase Aguda/análisis , Anticuerpos Antibacterianos/análisis , Citocinas/análisis , Disentería Bacilar/inmunología , Shigella sonnei/inmunología , Adolescente , Adulto , Células Productoras de Anticuerpos/inmunología , Antígenos Bacterianos/inmunología , Proteína C-Reactiva/análisis , Disentería Bacilar/etiología , Heces/microbiología , Femenino , Humanos , Interferón gamma/análisis , Masculino , Shigella sonnei/aislamiento & purificación , Factor de Necrosis Tumoral alfa/análisisRESUMEN
To address the hypothesis that increased infectious morbidity is associated with iron supplementation, 783 randomly selected infants were provided with a powdered full fat cow's milk (non-fortified group) and 872 with a powdered acidified full fat cow's milk fortified with 15 mg of iron as ferrous sulfate (fortified group). All infants were followed from birth to 15 months of age with a monthly home visit by a nurse who recorded morbidity occurring during the previous 30 days. At 9 months of age, 15% of infants in each cohort were receiving breast milk only; data for these infants were segregated to make the third group. Episodes (mean +/- SD) of diarrhea/infant/year were 1.06 +/- 1.29, 1.14 +/- 1.37, and 0.82 +/- 1.04 for the fortified, non-fortified and breast-fed groups, respectively; the fortified and non-fortified bottle-fed groups had a very similar incidence of respiratory illness; 2.66 +/- 2.07 and 2.74 +/- 2.24 episodes/infant/year, respectively. The incidence of respiratory illness for both bottle-fed groups was significantly higher than that for the breast-fed group (2.22 +/- 1.84 respiratory episodes/infant/year). We conclude that for the infants the tested form of iron fortified milk, which is sufficient to lower iron deficiency anemia, does not result in an increased incidence of diarrhea or respiratory illness.
Asunto(s)
Anemia Ferropénica/epidemiología , Diarrea Infantil/epidemiología , Alimentos Fortificados , Hierro , Leche , Infecciones del Sistema Respiratorio/epidemiología , Análisis de Varianza , Animales , Chile/epidemiología , Estudios de Cohortes , Femenino , Humanos , Incidencia , Lactante , Alimentos Infantiles , Recién Nacido , Masculino , Leche Humana , Estudios Prospectivos , Factores de Riesgo , Población UrbanaRESUMEN
Three siblings with alloimmune neonatal neutropenia are presented. An immunoglobulin G (IgG) antineutrophil antibody specific for NA-2 antigen was demonstrated in maternal serum and in both of the three affected infants who were studied as neonates. The mother's neutrophils were negative for NA-2 antigen. The father and all four children, including the three known to be affected, had neutrophils that expressed NA-2 antigen. One patient studied sequentially demonstrated an inverse relationship between the antineutrophil antibody titer and the absolute neutrophil count. Exchange transfusions did not appear to benefit two of the infants.
Asunto(s)
Inmunidad Materno-Adquirida , Inmunoglobulina G/análisis , Isoanticuerpos/análisis , Isoantígenos/inmunología , Neutropenia/congénito , Neutrófilos/inmunología , Especificidad de Anticuerpos , Recambio Total de Sangre , Femenino , Humanos , Inmunización , Huésped Inmunocomprometido , Recién Nacido , Isoantígenos/genética , Masculino , Neutropenia/genética , Neutropenia/inmunología , Neutropenia/terapia , Linaje , Embarazo/inmunologíaRESUMEN
We evaluated the effect of iron-supplemented milk on 86 healthy infants who were followed from 3 to 12 months of age. Whole milk was supplemented with 15 mg elementary iron as ferrous sulphate and 100 mg ascorbic acid per 100 g powder. 104 infants received the same milk with no supplement and served as control. All iron nutritional parameters were higher in the supplemented group at 9 and 12 months of treatment (p < 0.01). Iron-deficiency anemia was shown in 34% of the control as compared to 0% of the treatment group. The product exhibited excellent tolerance and could therefore be used to eradicate iron-deficiency anemia of the infant.
Asunto(s)
Anemia Hipocrómica/prevención & control , Alimentos Fortificados , Alimentos Infantiles , Hierro/administración & dosificación , Leche , Anemia Hipocrómica/epidemiología , Animales , Ácido Ascórbico/administración & dosificación , Chile/epidemiología , Estudios de Seguimiento , Humanos , Lactante , Estudios ProspectivosRESUMEN
We tested in the field an extruded rice flour, fortified with a bovine haemoglobin concentrate (Fe:14 mg/100 g of powder). This cereal has a high iron bioavailability, good protein quality and amino acid score. Healthy, term breast-fed infants were prospectively studied. One group (n = 92) received the fortified cereal (from 4 to 12 months of age). As control, 96 infants received regular solid foods (cooked vegetables and meat) from age 4 months. At the end of the field trial, a subsample of infants in both groups was supplemented with 45 mg Fe during 90 d. Iron nutrition status was determined at 9, 12 and 15 months. At 12 months, iron deficiency anaemia was present in 17 per cent of controls, in 10 per cent of fortified infants as a whole, but only in 6 per cent of the babies who consumed over 30 g of cereal/d. In addition, this latter group did not show any significant changes in iron nutrition status after the supplementation trial. Results demonstrate that the consumption of a haemoglobin fortified cereal is effective in markedly reducing the incidence of iron deficiency in breast-fed infants.
Asunto(s)
Lactancia Materna , Alimentos Fortificados , Hemoglobinas , Hierro/farmacocinética , Estado Nutricional , Disponibilidad Biológica , Humanos , Lactante , Estudios Prospectivos , Población UrbanaRESUMEN
To evaluate the effect of zinc on growth and immune function, 32 marasmic infants were selected on admission to the nutrition recovery center; 16 received 2 mg/kg daily of elemental zinc supplement as acetate and the remaining received a placebo. Immunity was assessed by skin-test response, T-cell blastic proliferation immunoglobulins, and infectious morbidity. Weight-for-length gain for initial 60 days in Zn-supplemented group was 9% of standard vs 3% for placebo (p less than 0.05). Energy intake was similar in both groups. Incidence of infections, especially pyoderma, was significantly higher in placebo group: 10 of 16 vs 3 of 16 in the supplemented group (p less than 0.025). Plasma Zn was correlated with number of febrile days in the prospective month (r = -0.66, p less than 0.05). The percent anergic infants decreased and serum IgA increased significantly only in Zn-supplemented group. Zinc supplementation has significant effects on weight gain and host defense mechanisms despite normal plasma levels. Zinc supplementation is recommended for optimal recovery from marasmus.
Asunto(s)
Crecimiento/efectos de los fármacos , Desnutrición Proteico-Calórica/terapia , Zinc/uso terapéutico , Antropometría , Formación de Anticuerpos/efectos de los fármacos , Femenino , Humanos , Inmunidad Celular/efectos de los fármacos , Lactante , Masculino , Desnutrición Proteico-Calórica/inmunología , Desnutrición Proteico-Calórica/fisiopatología , Zinc/sangre , Zinc/deficienciaRESUMEN
Para estudiar la función in vitro del leucocito PMN se estandarizaron las técnicas inmunológicas de capacidad fagocítica, opsónica y bactericida. La capacidad fagocítica se midió en sangre total, incubando leucocitos del sujeto en estudios en presencia de su propio plasma con estafilococos aureus muertos y la actividad opsónica se determinó incubando células de un individuo sano con plasma del sujeto en estudio. Los frotis teñidos se leyeron al microscopio de luz, y los resultados se expresaron como índice fagocítico, esto es número de bacterias ingeridas por 100 PMN. La capacidad bactericida se estudió, incubando una suspensión de leucocitos con bacterias (E. coli) en rotación continua a 37-C, basada en la técnica de Quie y cols. Se tomaron alícuotas para recuento de colonias por dilución en placa a los tiempos 0,20, 60 y 120 minutos. Los resultados se expresaron como índice bactericida, esto es, número de bacterias vivas a los 120 minutos/número de bacterias vivas a los 20 min. Para optimizar las técnicas se analizaron los siguientes parámetros: número de leucocitos/ml de sangre o suspensión, concentración y cepa de referencia de E. coli/ml de suspensión, período de incubación, reproducibilidad de la técnica, variabilidad intraindividual e interindividual y en el tiempo. Una vez estandarizados dichos parámetros, los índices de capacidad fagocítica y opsónica fueron de 9.2 ñ 0.85 y 8.1 ñ 0.6 (x ñ ESM), respectivamente. El índice promedio de la actividad bactericida fue de 0.14 ñ 0.05. Las pruebas fueron discriminatorias en pacientes con sospecha clínica de alteración de la capacidad funcional del leucocito
Asunto(s)
Adulto , Humanos , Masculino , Femenino , Bacteriólisis , Técnicas In Vitro , Neutrófilos/fisiología , Proteínas Opsoninas/análisis , Fagocitosis , Técnicas InmunológicasRESUMEN
In a double-blind, controlled, crossover study involving 47 subjects documented with seasonal allergic rhinitis, repeated intranasal administration of 4% sodium cromoglycate solution was associated with significant reduction in symptoms and decrease in consumption of antihistaminic drugs. Side effects were mild and transitory. It is concluded that intranasal sodium cromoglycate administration is an efficacious preventive and therapeutic approach in the management of patients with seasonal allergic rhinitis.