Genetic regulation of IgE responses: Achilles and the tortoise.

In the last few decades, basic biology and immunology have thrived, largely thanks to the use of model organisms that allow exploration of complex functions in ideal experimental conditions and genetically defined backgrounds. IgE regulation studies are no exception to this rule. The current challenge is to anchor what we are learning in test tubes and animals to mechanisms of disease in patients with allergy. With information about the human genome rapidly piling up, and strong associations between single nucleotide polymorphisms and disease phenotypes reported more and more often, it is becoming clear that such anchoring cannot occur without a robust integration between the biology of model systems and the biology of natural genetic variants. Here we will argue that an essential component of this integration is the functional analysis of the mechanisms through which natural variation affects pathways relevant to the pathogenesis of IgE-dependent inflammation.