Infant Immune Response to Bacterial Infection

Overview

This study will examine the response of white blood cells to bacterial infection in blood taken from the umbilical cords of newly delivered infants. The blood samples will be taken from both male infants who were carried to term and male infants who were born prematurely, and genetic studies will compare these blood samples to samples drawn from healthy adult male volunteers. The study is designed to look at the ways in which the immune systems of newborn infants respond to bacterial infection. Participants in this study will be pregnant Chinese women admitted to the labor ward of the Prince of Wales Hospital (Sha Tin district of New Territories, Hong Kong SAR) for normal spontaneous delivery. Those with known blood-borne infectious diseases such as HIV and hepatitis B will be excluded from this study. Cord blood and placenta samples will be collected after the completion of delivery. The samples collected for this study will be restricted to male newborns. A comparison group of blood samples will be drawn from healthy male adults between 25 and 35 years of age....

Bacterial infection in preterm neonates is a significant clinical problem. Neutrophils play a critical role in the bactericidal process, which is immature in newborns though their peripheral blood neutrophil counts are similar to or higher than that of older children and adults. The use of steroids to enhance lung maturation in premature infants complicates this problem. Many studies have shown different biological activities between lipopolysaccharide (LPS) activated neonatal cord blood neutrophils and adult peripheral blood neutrophils. In spite of a number of previous studies, the genetic basis of this differential response to LPS-activation remains unknown. In this study, we will identify the differential gene expression profiles of LPS-activated adult peripheral blood versus cord blood neutrophils from both term and preterm infants by whole genome ligonucleotide microarray. We will investigate the priming effect of histologic chorioamnionitis (HCA), a severe infection/inflammation implicated in many neonatal diseases, on the immune response in neutrophils in terms of gene expression. The effect of prenatal administration of steroids on the immune response in preterm neutrophils is another question we will address in the proposed study. This study will provide insight into the molecular basis for genetic regulation of neutrophil development. We expect to identify novel genes with differential expressions in LPS-activated cord blood neutrophils when compared to those of LPS-activated adult cells. Aberrant transcripts due to the priming effect of HCA to the immune response in term neutrophils will also provide insight on the defense mechanism of subsequent exposures to bacterial infection. This is a collaborative study. All samples will be collected by our Collaborators at the Chinese University of Hong Kong, Hong Kong. We will perform expression profiling in the Laboratory of Clinical Genomics at NICHD. This protocol has been approved by the Joint Clinical Research Ethics Committee of the Chinese University of Hong Kong and Hospital Authority of Hong Kong.