Substantial increases in asthma have occurred among children age 0-4 years and urban ethnic minorities. Exposures to allergens critical to the onset of asthma may occur at a very young age, as suggested by the finding that children with elevated immunoglobulin E (IgE) levels at age 9 months are predisposed to recurrent wheezing and positive allergy skin tests by age 6 years. In addition, cord blood mononuclear cells (CBMC) have been shown to proliferate following in vitro stimulation to multiple antigens. Dust mite and ovalbumin - specific neonatal T cells clones have been derived and genotyped, confirming their fetal origin. These results suggest that sensitization may even occur prenatally. However, acceptance of CBMC antigen-induced proliferative responses as signifying in utero sensitization has been questioned, in part because the mechanism of T cell priming has not been demonstrated and specificity of these in vitro responses has not been proven. We hypothesize that in utero sensitization occurs. To demonstrate in utero sensitization, we will determine whether neonatal T cell priming occurs to influenza antigens administered prenatally by vaccination of the pregnant mother. Influenza-specific T cells will be measured by applying tetramer technology. We also hypothesize that increased asthma severity and/or increased T helper 2 (Th2) polarization during pregnancy may influence Th polarization in the newborn and young child. To study these prenatal events, we will recruit pregnant women with atopic asthma and compare the Th2 status and asthma severity of the mother during pregnancy with the Th2 status of the newborn. Th2 status will be evaluated by multiple biomarkers, including IgE levels, intracytoplasmic cytokines, and chemokine levels. To determine the impact of molecular biomarkers for Th2 immune responses at birth on the risk for atopy during early childhood, newborns will be followed prospectively through age 5 years. Both clinical (i.e., history of recurrent wheezing, physician diagnosis of asthma) and immunological (i.e., total and allergen-specific IgE, cytokine levels) endpoints will be evaluated. Identifying critical biomarkers at birth or at the earliest possible time would in turn provide the greatest opportunity for early identification of children at increased risk for allergies, including asthma.
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