Altered frequency and phenotype of CD4+ forkhead box protein 3+ T cells and its association with autoantibody production in human immunodeficiency virus-infected paediatric patients.

The association between immune dysfunction and the development of autoimmune pathology in patients with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) is not clear. The frequency and phenotype of regulatory T cells, as well as the presence of autoantibodies, were evaluated in a paediatric cohort of HIV-infected patients without clinical evidence of autoimmune disease. Lower absolute counts but higher percentages of total CD4(+) forkhead box protein 3 (FoxP3)(+) T cells were recorded in children with severe immunosuppression than in those without evidence of immunosuppression. The frequencies of classical CD4(+) CD25(+) FoxP3(+) regulatory T cells were not altered, whereas CD4(+) FoxP3(+) CD25(-) T cells were found increased significantly in patients with severe immunosuppression. Like classical regulatory T cells, CD4(+) FoxP3(+) CD25(-) T cells display higher cytotoxic T-lymphocyte antigen 4 (CTLA-4) but lower CD127 expression compared with CD4(+) FoxP3(-) CD25(+) T cells. An improvement in CD4(+) T cell counts, along with a decrease in viral load, was associated with a decrease in CD4(+) FoxP3(+) CD25(-) T cells. The majority of the patients with severe immunosuppression were positive for at least one out of seven autoantibodies tested and displayed hypergammaglobulinaemia. Conversely, HIV-infected children without evidence of immunosuppression had lower levels of autoantibodies and total immunoglobulins. A decline in CD4(+) FoxP3(+) T cell numbers or a variation in their phenotype may induce a raise in antigen exposure with polyclonal B cell activation, probably contributing to the generation of autoantibodies in the absence of clinical autoimmune disease.

Expresión de L-selectina en linfocitos T y neutrófilos de niños infectados con HIV / L-selectin expression on T lymphocytes and neutrophils in HIV infected children

La capacidad de los leucócitos de abandonar la circulación y migrar hacia los tejidos es un paso crítica de la respuesta inmune. La L-selectina, selectina leucocitaria (CD62L), media la unión de linfócitos a las vÛnulas endoteliales altas de los ganglios linfáticos periféricos, y también participa en la adhesión de linfócitos, neutrófilos y monócitos al endotelio vascular activado en los sítios de inflamación. En este trabajo se estudiaron los niveles de expresión de L- selectina sobre los linfócitos T y polimorfonucleares neutrófilos en 25 niños HIV (+) sin tratamiento antirretroviral y 25 niños sanos HIV (-), avaluando además su comportamiento en 10 de los pacientes, luego de 6 meses de iniciada la terapéutica específica para el HIV. El número de linfócitos TCD3+, CD4+ y CD8+ que expresan CD62L se encontró significativamente disminuido en los niños HIV(+) con respecto al grupo control. El porcentaje de neutrófilos que expresan CD62L se encontro significativamente disminuido en los pacientes con mayor compromiso inmunológico. Se observó una correlación positiva entre los niveles de LTCD4+ y el porcentaje de neutrófilos que expresan CD62L. Luego de 6 meses de tratamiento antirretroviral no hubo cÔmbios significatios en los niveles de expresión de CD62L sobre LTCD4+ y LTCD8+ . La reducción en los niveles de expresión de L-selectina en estos tipos celulares sugiere que durante la infección por HIV las funciones leucocitarias tales como la migración y el asentamiento linfocitario son anormales, contribuyendo al progresivo deterioro inmune. (AU)

Expresión de L-selectina en linfocitos T y neutrófilos de niños infectados con HIV / L-selectin expression on T lymphocytes and neutrophils in HIV infected children

La capacidad de los leucócitos de abandonar la circulación y migrar hacia los tejidos es un paso crítica de la respuesta inmune. La L-selectina, selectina leucocitaria (CD62L), media la unión de linfócitos a las vênulas endoteliales altas de los ganglios linfáticos periféricos, y también participa en la adhesión de linfócitos, neutrófilos y monócitos al endotelio vascular activado en los sítios de inflamación. En este trabajo se estudiaron los niveles de expresión de L- selectina sobre los linfócitos T y polimorfonucleares neutrófilos en 25 niños HIV (+) sin tratamiento antirretroviral y 25 niños sanos HIV (-), avaluando además su comportamiento en 10 de los pacientes, luego de 6 meses de iniciada la terapéutica específica para el HIV. El número de linfócitos TCD3+, CD4+ y CD8+ que expresan CD62L se encontró significativamente disminuido en los niños HIV(+) con respecto al grupo control. El porcentaje de neutrófilos que expresan CD62L se encontro significativamente disminuido en los pacientes con mayor compromiso inmunológico. Se observó una correlación positiva entre los niveles de LTCD4+ y el porcentaje de neutrófilos que expresan CD62L. Luego de 6 meses de tratamiento antirretroviral no hubo câmbios significatios en los niveles de expresión de CD62L sobre LTCD4+ y LTCD8+ . La reducción en los niveles de expresión de L-selectina en estos tipos celulares sugiere que durante la infección por HIV las funciones leucocitarias tales como la migración y el asentamiento linfocitario son anormales, contribuyendo al progresivo deterioro inmune.

[Behavior of soluble L-selectin in HIV infected children]. / Comportamiento de la forma soluble de L-selectina en niños infectados con HIV.

L-selectin is an adhesion molecule that is responsible for the initial attachment of leukocytes to endothelium. After leukocyte activation L-selectin is endoproteolytically released from the cell surface. In order to analyze the relationship between soluble L-selectin (sL-selectin) and parameters of immune activation and disease progression, 51 HIV infected children and 15 healthy controls were studied. Serum L-selectin concentrations were significantly higher in HIV infected children than in the control group. Levels of sL-selectin were higher in HIV infected patients with severe immunologic suppression than in those with moderate or no evidence of suppression. A positive correlation between sL-selectin levels and LTCD8 counts, sL-selectin and soluble intercellular adhesion molecule-1 (sICAM-1) and immunogobulin A (IgA) levels was detected. On the contrary sL-selectin concentration did not correlate with plasmatic viral load. The correlation with parameters of immune activation may implicate involvement of sL-selectin in the immunopathogenesis of HIV infection.

Comportamiento de la forma soluble de L-selectina en niños infectados con HIV. / [Behavior of soluble L-selectin in HIV infected children]

L-selectin is an adhesion molecule that is responsible for the initial attachment of leukocytes to endothelium. After leukocyte activation L-selectin is endoproteolytically released from the cell surface. In order to analyze the relationship between soluble L-selectin (sL-selectin) and parameters of immune activation and disease progression, 51 HIV infected children and 15 healthy controls were studied. Serum L-selectin concentrations were significantly higher in HIV infected children than in the control group. Levels of sL-selectin were higher in HIV infected patients with severe immunologic suppression than in those with moderate or no evidence of suppression. A positive correlation between sL-selectin levels and LTCD8 counts, sL-selectin and soluble intercellular adhesion molecule-1 (sICAM-1) and immunogobulin A (IgA) levels was detected. On the contrary sL-selectin concentration did not correlate with plasmatic viral load. The correlation with parameters of immune activation may implicate involvement of sL-selectin in the immunopathogenesis of HIV infection.

Prognostic value of soluble intercellular adhesion molecule-1 (s-ICAM-1) in HIV-infected children.

Central events in the host defence system and immune-mediated damage are tightly regulated by cell adhesion molecules. Sera from 28 human immunodeficiency virus (HIV)-1 infected children divided into groups according to disease severity, six seroreverting (SR) children and 25 healthy controls were studied to detect the presence of soluble intercellular adhesion molecule-1 (s-ICAM-1). Soluble ICAM-1 levels were found to be significantly increased in HIV-infected children in comparison with SR children or healthy controls. Levels of soluble ICAM-1 were higher in patients with severe forms of HIV-infection than in those with a milder form of the disease. Significant differences in titers of s-ICAM-1 were recorded between SR children and HIV-infected children with mild disease or healthy controls. There was a significant correlation between s-ICAM-1 levels and the concentrations of beta 2 microglobulin (beta 2m) and, to a lesser extend, immunoglobulin A levels (IgA). Soluble ICAM-1 levels didn't change considerably in HIV-infected children in stable clinical conditions, independently of their clinical stage of the disease, during a follow-up period of 9-12 months. Conversely, s-ICAM-1 levels increased simultaneously with the appearance of new well-defined clinical disorders or decreased during the improvement of clinical conditions. A significant negative correlation was recorded between the titers of the s-ICAM-1 and the CD4(+) T-cell levels. These results suggest that the s-ICAM-1 might be another useful tool to evaluate disease progression.

Soluble intercellular adhesion molecule-1 in paediatric connective tissue diseases.

The intercellular adhesion molecule-1 (ICAM-1) is a cytokine-induced glycoprotein involved in the recruitment of cells into tissues undergoing inflammatory responses. The aim of this study was to compare the levels of soluble ICAM-1 (s-ICAM-1) in children with juvenile chronic arthritis (JCA) and systemic lupus erythematosus (SLE) and to evaluate the usefulness of this molecule as marker of disease activity. Levels of s-ICAM-1 were measured in sera using a monoclonal antibody sandwich enzyme-linked immunoassay. Serum levels (mean+/-SD) of s-ICAM-1 in 37 children with JCA, 18 patients suffering from SLE and 25 healthy controls were 609+/-184, 513+/-139 and 210+/-95 ng/ml, respectively. A significant difference could be demonstrated between the levels of s-ICAM-1 in sera from each disease, as a group, and those of healthy controls. Higher levels of s-ICAM-1 were recorded in JCA patients with systemic features and patients who had polyarthritis than in children who were pauciarticular. A positive correlation was observed between s-ICAM-1 levels and disease activity score in SLE patients. Moreover, s-ICAM-1 levels closely followed clinical conditions in five children with SLE during follow-up. The data show that s-ICAM-1 levels are increased in children suffering from connective tissue diseases and reflect disease status or activity, suggesting the usefulness of this molecule in the follow-up of these diseases.

[Soluble intercellular adhesion molecule-1 (ICAM-1) levels in HIV infected children]. / Niveles séricos de la forma soluble de la molécula de adhesión intercelular 1 (s-ICAM-1) en la infección por HIV en niños.

Intercellular adhesion molecule-1 (ICAM-1) is a membrane bound molecule that is involved in cell to cell adhesive interactions within the immune system. The aim of this study was to measure the concentrations of soluble ICAM-1 (s-ICAM-1) in 25 HIV-1 infected pediatric patients. We compared s-ICAM-1 values to parameters of immune activation--such as IgA and beta 2 microglobulin (beta 2 m) and viral replication such as adenosine deaminase (ADA). s-ICAM-1 levels were found to be significantly increased in HIV-1 infected children when compared with healthy controls. Levels of s-ICAM-1 were higher in patients with severe forms of HIV-1 infection in comparison with those with a mild form of the disease or non symptomatic infection. No differences in titers of s-ICAM-1 were recorded between seroreverters and healthy controls. A positive correlation between levels of s-ICAM-1 and IgA, beta 2 m or ADA concentrations was detected. Similarly, there was statistically significant correlation between levels of IgA, beta 2 m or ADA. In conclusion, increased s-ICAM-1 levels in HIV-1 pediatric patients appeared to be another important feature among the immune disturbances triggered by HIV-1 infection. s-ICAM-1 might be involved in the development of the immunologic dysfunction during the progression of the disease.

Niveles séricos de la forma soluble de la molécula de adhesión intercelular 1 (s-ICAM-1) en la infección por HIV en niños. / [Soluble intercellular adhesion molecule-1 (ICAM-1) levels in HIV infected children]

Intercellular adhesion molecule-1 (ICAM-1) is a membrane bound molecule that is involved in cell to cell adhesive interactions within the immune system. The aim of this study was to measure the concentrations of soluble ICAM-1 (s-ICAM-1) in 25 HIV-1 infected pediatric patients. We compared s-ICAM-1 values to parameters of immune activation--such as IgA and beta 2 microglobulin (beta 2 m) and viral replication such as adenosine deaminase (ADA). s-ICAM-1 levels were found to be significantly increased in HIV-1 infected children when compared with healthy controls. Levels of s-ICAM-1 were higher in patients with severe forms of HIV-1 infection in comparison with those with a mild form of the disease or non symptomatic infection. No differences in titers of s-ICAM-1 were recorded between seroreverters and healthy controls. A positive correlation between levels of s-ICAM-1 and IgA, beta 2 m or ADA concentrations was detected. Similarly, there was statistically significant correlation between levels of IgA, beta 2 m or ADA. In conclusion, increased s-ICAM-1 levels in HIV-1 pediatric patients appeared to be another important feature among the immune disturbances triggered by HIV-1 infection. s-ICAM-1 might be involved in the development of the immunologic dysfunction during the progression of the disease.

Retrospective study of children born to HIV-1-infected mothers in a pediatric hospital in Argentina.

The aim of this retrospective study, which included 103 children born to human immunodeficiency virus type 1 (HIV-1)- infected mothers, is to initiate a database on HIV-infected children, which has to date been unavailable in Argentina. All HIV-1 seropositive children admitted to the Pedro de Elizalde Children's Hospital in Buenos Aires from March 1, 1987, to December 31, 1992, were enrolled in this study. The number of patients enrolled dramatically increased each year during the period of study. Of the 60 infected children, 22 (36.66%) have died with a clinical diagnosis of HIV-1 infection; in 10 of those children HIV infection was also confirmed by P24 antigenemia and/or polymerase chain reaction (PCR): 20 qualified for the Centers for Disease Control and Prevention (CDC) P2D class (P2D1 = 7, P2D2 = 10, P2D3 = 3), 1 for P2C, and 1 for P2A, whose cause of death was pneumonia. The mean age of death was 14.8 months, 18 (82%) died before 18 months. When immunoglobulin G (IgG), IgM, and IgA levels were determined according to age and clinical status, significant differences (P < 0.005) were observed when both asymptomatic and symptomatic infected children (P1, P2) were compared with noninfected children (P3). A significant difference was also obtained between those children who qualified for P2 classification prior to 12 months of age who died early (at or prior to 25 months) and those who reached stage P2 after 12 months of age and have survived to date (X2 = 24.73, p < 0.0001; RR = 5.83, 2.52 < RR < 13.49).