The genetic and environmental basis of atopic diseases

The prevalence of atopic diseases has increased abruptly in recent years in most Westernized societies, making the question why this happened the topic of a heated debate. The best paradigm available to date to explain this steep rise, the 'hygiene hypothesis', supports that it is the excess 'cleanliness' of our environments that has led to the decline in the number of infectious stimuli that are necessary for the proper development of our immune system. Recent findings support that it is the combined effect that not only pathogenic, but also non-pathogenic microorganisms, and even their structural components, can exert on the immune system that deters from the development of atopic responses. Adding to these results are intriguing new findings on the effect different gene polymorphisms can have on an individual's predisposition to allergic diseases. The most important linkages produced, to date, include those among the genes for IL-4, IL-13, HLA-DRB, TNF, LTA, FCER1B, IL-4RA, ADAM33, TCR alpha/delta, PHF11, GPRA, TIM, p40, CD14, DPP10, T-bet, GATA-3, and FOXP3 and allergic disorders. The two parallel research efforts, epidemiologic and genetic, are only recently starting to converge, producing fascinating results on the effect particular gene-environment interactions might have in the development of atopy. The most important lesson learned through this tremendous research effort is that not only a small number but thousands and millions of separate risk factors act in concordance in the production of the allergic phenotype.