Research Project
6184545
There has been a five-fold increase in the prevalence of asthma over the last 25 years in the UK. The impact of this on quality of life, health and on the health economy is a major concern for medical services. Much evidence points to early life as a critical period during which allergic sensitization occurs to be followed years later by the onset of disease. We propose to investigate the hypothesis that the critical period for sensitization occurs in early fetal life and is affected by the health, nutrition and environment of the mother. If the increasing prevalence of asthma is to be reversed, then detailed study of the origins of atopy in fetal life and the subsequent development of disease is essential. The ultimate aim of such studies will be to identify avoidable factors and targets for intervention which might lead to the establishment of a primary prevention programme. There will be 8 components to the research programme. The first will determine if allergen can be detected in matched maternal plasma, umbilical cord plasma and amniotic fluid, and the influence of this on allergic sensitization in utero and subsequent disease development. Aim 2 will further elucidate the pathway by which IgE and allergen are transferred to the amniotic fluid while Aim 3 will determine the phenotype of the tissue resident and circulating antigen-presenting cells in the human fetus, followed by functional studies to determine if fetal antigen presenting cells can take up, process, and present antigen in an IgE dependent manner. This will be associated with an investigation of the phenotype of allergen specific T-cells in the fetal circulation and the contribution of the gestation associated tissues to the cytokine milieu encountered by the fetus. Aim 7 will determine if maternal infection with respiratory syncytial virus during pregnancy influences the development of allergic disease and finally Aim 8 will evaluate the relationship between the composition of phospholipids incorporated into cell membranes and antigen presenting cell function. By identifying the pathway of IgE dependent sensitization and mechanisms by which fetal immune responses to allergen can be manipulated, we aim to identify targets for future therapeutic intervention.
