IgE, allergies and helminth parasites: a new perspective on an old conundrum

This paper analyses the association between infection with helminth parasites, the elevated production of IgE and the expression of allergies. Interpretations of this interaction have taken place in a scientific environment whose most secure element is the immunochemistry of allergic reactions resulting in a substantial body of literature that has sought a biological role for allergic reactivity in protective immunity directed against helminth parasites. While the association between helminth infections and elevated levels of IgE, mast cells and eosinophils is well established, a functional role for allergic reactions in protection against helminths has eluded experimental proof. Instead of this hypothesis, it is proposed that allergic reactivity is rarely present in helminth-infected individuals because allergic reactions do not function to regulate helminth infections. Data from many sources are used to establish that the 'normal' state of all mammals is to be infected with helminth parasites from shortly after birth until well into adulthood. Only in the last 100 years or so have people living in areas of high development with sophisticated water and sewage systems been able to escape helminth infection. Allergies are as conspicuously present in these human populations as they are absent in populations that are still regularly exposed to helminths. Furthermore, in populations with endemic helminthoses there is little overt expression of allergic pathology that could be connected to the acquisition or elimination of helminth parasites. Based on these observations, it is suggested that endemic helminthoses activate the Th2 system, particularly at mucosal surfaces, to provide a different level of immunological homeostasis than currently occurs in developed societies. Under these conditions, mast cells, eosinophils and IgE rarely participate in reactions that we would recognize as 'allergic', although their participation in the control of helminth infections is still envisaged. Allergic reactions are considered to be a purely pathologic consequence of the disruption of this homeostatic mechanism and are not protective at all for the individual expressing them. This interpretation is derived from the immunobiology of the host-parasite interaction rather than the biology of allergies and should lead to new concepts regarding both allergic disease and the role of helminth infections in human and animal populations.