The Hapten-Atopy hypothesis II: the 'cutaneous hapten paradox'.
ABSTRACT One explanation for the striking increase in atopic disease in developed countries over the last 50 years has been the 'Hygiene Hypothesis'; a reduced exposure to pathogenic microorganisms. We have postulated previously that oral and cutaneous exposure to chemicals generally and to haptens in particular, may have also contributed to the increased prevalence of atopic disease; the 'Hapten-Atopy Hypothesis'. The purpose here is to extend further that hypothesis by consideration of the impact interplay between the innate and adaptive immune systems may have on the development of atopic allergy. It is clear that experimental cutaneous exposure to hapten can generate immune responses of different types with regard to T-helper (Th) cell phenotype. Allergic contact dermatitis is frequently associated with a selective Th1 (and Tc1)-driven inflammation, whereas atopic dermatitis is characterized by preferential Th2 cell responses. We postulate here that initial innate immune responses to chemical haptens result in the promotion of Th1 cell responses secondary to stimulation of Toll-like receptor. However, we argue also that under conditions where there is prolonged skin exposure to hapten there will be a shift of Th cell phenotype to selective Th2-type responses. The significance of such interactions is the possibility that repeated low-level skin exposure to certain types of hapten may result in the creation of an immunological environment in which the development of Th2 immune responses to third party antigens is favoured. The hypothesis is advanced that the nature and conditions of skin exposure to common haptens may impact on the quality of cutaneous immune responses such that in some circumstances the development atopic disease is favoured.
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ABSTRACT: Growing Up in Singapore Towards healthy Outcomes (GUSTO) is Singapore's largest birth cohort study to date. The main aim of GUSTO is to evaluate the role of developmental factors in the early pathways to metabolic compromise. Detailed data is collected for a range of environmental exposures in the parents and offspring, and allergic disorders are among a number of outcomes assessed in infancy and childhood. Under the Allergy domain of GUSTO, this integrated study will describe the epidemiology of allergic manifestations and different phenotypes in the Asian context and help shed light on the association of metabolic disease to allergy. Epigenetic mechanisms and associations with other childhood disorders will also be explored. The aim of this report is to focus on methodology of GUSTO, and to suggest similar approaches (i.e., integrated cohort studies on pediatric allergy) worldwide. Recruitment commenced in 2009 with a cohort of 1,163 pregnant mothers in their first trimester. The mothers and children were followed throughout pregnancy and follow-up will continue until the child reaches 3 years of age. Preliminary results showed that 39.8% of the mothers had a personal history of having at least one allergic disease, which included asthma, eczema and allergic rhinitis. Further data collection and analyses are still ongoing. Allergy is a complex spectrum of disorders with numerous poorly-understood aspects. The ongoing GUSTO cohort study, with its longitudinal design and multi-disciplinary nature, may provide new insights into developmental influences on allergy. As a Singapore-based study, it will be the first integrated allergy cohort in Southeast Asia, of which recruitment started during pregnancy.Asia Pacific allergy. 04/2012; 2(2):144-8.