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Immune Tolerance

Modulation of IgE mediated diseases in children : atopic asthma as a paradigm

patrick holt
Patrick G Holt DSc, FAA
Telethon Institute for Child Health Research, Perth

Current treatment paradigms for atopic asthma focus on normalisation of immunological and/or lung function in subjects with established disease. This approach has a range of theoretical limitations, including the decreasing plasticity of T-cell memory responses over time which limit the effectiveness of immunotherapy, the parallel decreasing reversibility of changes in lung function over time, and the ever widening range of environmental factors capable of triggering exacerbation of symptoms as the disease progresses. This presentation will review arguments in favour of an alternative approach i.e. intervention at very early stages of disease before chronicity becomes established. The target age group of principal interest in this context are preschool children and/or those in early primary school. The underlying theoretical basis for the interventions to be discussed is provided by recent findings from birth cohort studies. Notably, a series of studies indicate that both early sensitisation to inhalant allergens and early lower respiratory tract viral infections independently increase risk for development of persistent asthma by the end of the preschool years. Additionally, these two inflammatory pathways can interact synergistically to generate very high Odds Ratios for asthma at 5-6 years, and hence attenuation of either pathway has the potential to have a significant impact on disease prevalence within the population at large. A series of plausible intervention strategies will be discussed, based on recent findings related to asthma aetiology. The targets for these strategies include the maturation process underlying the postnatal acquisition of overall immune competence, development and consolidation of allergen-specific Th-memory, and airways inflammation in infants and young children triggered by atopic responses to inhalant allergens and/or responses to viral pathogens.


Holt PG, Sly PD, Martinez FD, Weiss ST, Björkstén B, von Mutius E, Wahn U. Drug development strategies for asthma: in search of a new paradigm. Nature Immunol 2004, 5:695-698.

Holt PG, Upham JW and Sly PD. Contemporaneous maturation of immunological and respiratory functions during early childhood: implications for development of asthma prevention strategies. JAllergy Clin Immunol 2005, 116:16-24.

Slide presentation

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