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IntroductIon: current advances in neonatology have improved survival among preterm and low-birth-weight infants. however, the risk of neonatal death in preterm infants is much greater than in full-term neonates and is frequently associated with infections. Methods: Little is known about the immune status of preterm neonates; therefore, we analyzed the frequency and absolute counts of different immune populations in 211 cord blood samples taken from very-preterm to full-term neonates. results: We found that absolute counts of all the immune subsets analyzed (i.e., monocytes, granulocytes, B cells, natural killer (NK) cells, cD4 + , and cD8 + T cells) were markedly lower in preterm infants than in full-term infants. surprisingly, we observed that regulatory T cells (Tregs) were the only cell subset that did not decrease in preterm infants, and their frequency was even higher than in full-term infants. dIscussIon: Tregs are crucial to maternal-fetal tolerance, but their suppressive role could be also implicated in the leukopenia observed in preterm infants. We did not observe differences in thymic function, but we found that plasma levels of interleukin (IL)-7 and the frequency of its receptor were significantly decreased in preterm infants. Our results could help to identify leukopenia and to implement immune therapies that significantly diminish mortality in preterm neonates. r ecent developments in neonatology and improvements in technology to manage preterm neonates have significantly increased the survival of very-preterm neonates (less than 28 wk of gestation) and very-low-birth-weight infants (less than 1,500 g) (1). However, the relative risk of neonatal death is much greater for preterm infants than for full-term infants, and prematurity has become the leading cause of perinatal morbidity and mortality (2,3). Along with decreasing gestational age (GA), low birth weight is also associated with increased perinatal morbidity and mortality (4). Among the causes responsible for this increased mortality, neonatal sepsis and bronchopulmonary dysplasia are the most frequent causes of death in premature newborns (3).In fact, the most important factors that predispose to infection are prematurity and/or low birth weight.Little is known about innate immunity in premature neonates and the capacity of their immune systems to fight against infections. Several authors have reported differences in phenotype and function of lymphocytes between healthy newborns, children, and adults (5). The immune response of preterm infants is assumed to be immature, although quantitative data on differences in immune capacity between preterm and full-term infants are scant.The objective of this study was to investigate whether the high incidence of infections in preterm infants could be due to an immunodeficiency and, if so, to identify which immune cell populations are implicated in the absence of an adequate immune response. We performed a comprehensive analysis of the frequency and absolute counts of several cell populations in preter...

We have investigated the relationship between disease progression and several immunologic and virologic markers of HIV infection. Plasma samples from infants born to HIV-1-infected mothers were collected at birth and at 1, 2, 4, 6, 9, 12, 15, and 18 mo of age and subsequently were assayed every 6 mo for viral load, viral phenotype, and lymphocyte populations. A cutoff level of 25% indicative of a preserved immunologic status, both of CD4+ and CD8+ blood T cells, was associated with significant differences in disease progression (p = 0.04 and 0.02, respectively). Infants with median CD4+ T cells <25% had a relative risk of progression to AIDS 3.35-fold higher than those with CD4+ above this level (p = 0.05). The relative risk of progression to AIDS for infants with median CD8+ <25% was 4.95-fold higher than for those with CD8+ percent above this threshold (p = 0.03). Similarly, a cutoff level of viral load of 5.5 log10 copies/mL was indicative of a worse prognosis. Infants with median viral load >5.5 log10 copies/mL had a relative risk of progression to AIDS 23.72-fold higher (p = 0.0001) than those with median viral load below this threshold. Interestingly, changes from a slow replication and low titer to a rapid replication and high titer of virus and from nonsyncytium-inducing to syncytium-inducing viral phenotype were indicative of progression to AIDS. Our results indicate that biologic phenotype of viral isolates and CD8+ T-lymphocyte percentages in peripheral blood as well as viral load and CD4+ T-lymphocyte percentages could predict rapid progression to advanced HIV-1 disease in HIV-1-infected infants.

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ABSTRACT. Objective. Human immunodeficiency virus type 1 (HIV-1)-associated progressive encephalopathy (PE) is a common and devastating complication of HIV-1 infection in children, whose risk factors have not yet been clearly defined. Regardless of the age of presentation, PE shortens life expectancy. Paradoxically, as survival of patients has been prolonged as a result of the use of antiretroviral therapy, the prevalence of PE has increased. Therefore, a predictive marker of PE emergence is critical. The objective of this study was to determine in an observational study whether any immunologic (CD4 ؉ and CD8 ؉ T-lymphocyte counts, monocyte counts) or virologic (viral load [VL], biological characteristics of viral isolates) marker might be predictive of PE and whether any particular marker may be involved in the timing of clinical onset of PE.Methods. A total of 189 children who were vertically infected with HIV-1 were studied retrospectively, 58 of whom fulfilled criteria of the American Academy of Neurology for PE. T-lymphocyte subsets and monocytes in peripheral blood were quantified by flow cytometry. HIV-1 RNA was measured in plasma using a quantitative reverse transcriptase polymerase chain reaction assay. Demographic, clinical, and viro-immunologic characteristics in infants were compared with control groups using logistic regression. Proportions were compared using the 2 test or Fisher exact test. For each child, immunologic and virologic markers were analyzed in parallel closely before clinical onset of PE and closely after PE onset and compared by using the Student t test for paired samples.Results. Overall, mortality of 58 HIV-1-infected children who developed PE was significantly higher than of children who did not develop this complication. Blood CD8 ؉ T-lymphocytes <25% in the first months of life suggested a relative risk of progressing to PE 4-fold higher than those with CD8 ؉ >25% (95% confidence interval: 1.2-13.9) and remained statistically significant after adjustment for treatment. When we compared the PE-positive group with the acquired immunodeficiency syndrome (AIDS)/PE-negative group (children who developed clinical category C and without neurologic manifestations) in a cross-sectional study within 12 months before PE or AIDS diagnosis, respectively, the %CD8 ؉ T-lymphocytes were significantly lower in the PE-positive group. Normalized absolute counts of CD8 ؉ T-lymphocytes with respect to seroreverting children were significantly lower in the group of children with encephalopathy with respect to the AIDS/PE-negative group (data not shown). It is interesting that a statistically significant increase was observed in circulating monocyte percentages and absolute counts shortly before the first neurologic symptoms compared with values after PE was established and with those from HIV-1-infected controls. With respect to AIDS-related events, PE was strongly associated with anemia and lymphoid interstitial pneumonitis in the PE-positive group with respect to a group of children with AIDS but w...