1. Understanding the mechanism underlying
food allergy development
Both genetic and environmental factors influence the maintenance
of immune homeostasis and the development of food allergy.
When the immune system in early life encounters food antigens
genetic, environmental and dietary influences lead to an immune
response where either tolerance develops to the antigen or
an immune activation and hypersensitivity results. We are
assessing immune response profiles after introduction of food
antigens in early life. The foods we focus on include egg
and cow's milk proteins, to which resolution of allergy usually
occurs over time, and peanut, which frequently results in
lifelong hypersensitivity and potential anaphylaxis. We focus
our research on the development of oral tolerance, the importance
of breast milk and timing of the introduction of solid food
antigens for programming the developing immune response.
We hypothesise that early antigen exposure to food antigens
at an appropriate dose and time in early postnatal life, will
promote the establishment of regulatory mechanisms in the
developing gut immune system, particularly in breast fed infants
and decrease the potential for allergy development.
We have demonstrated that early food antigen exposure in
the presence of maternal milk results in a down-regulated
immune antibody response to egg ovalbumin (OVA), (Figure 1),
a reduction in markers associated with allergy and an increase
in immune markers associated with tolerance induction such
as transforming growth factor beta and SMAD expression (Figure
2). Intermittent OVA exposure induced immuno-regulatory markers
only in the local gut environment but not systemically, where
as continuous daily OVA exposure commencing in early life
induced tolerance in the local gut environment as well as
in the periphery. The data highlights the importance of introducing
food antigens early in life in the presence of breast milk
for programming the infant immune response toward tolerance
induction.
We are also assessing tolerance induction in infants in a
clinical trial (STEP) as part of a new collaboration with
Prof Makrides (Applied Nutrition). Timing of the introduction
of egg into the diet of infants at risk of allergy development
is being assessed.
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