Parasite-induced ‘nonspecific’ IgE does not protect against allergic reactions

Abstract

High levels of immunoglobulin E (IgE) are produced in animals, including man, infected with helminth parasites^1,2. Such infection results not only in the production of parasite-specific IgE but also, through polyclonal stimulation of IgE-B cells, in the production of a large excess of parasitic nonspecific IgE³. IgE antibodies mediate allergic reactions by binding to receptors on the plasma membrane of mast cells, which are then said to be sensitised; subsequent attachment of antigen to the membrane-bound antibody causes cross-linking of the receptors leading to the release of histamine and other active substances⁴. Mast cells can be passively sensitised both in vivo and in vitro and passive sensitisation with a specific IgE antibody may be inhibited by prior saturation of IgE receptors with an excess of ‘nonspecific’ IgE^5,6. In this way, helminth-infected animals become refractory to passive sensitisation, as do animals bearing IgE myelomas, because of the pre-emption of mast-cell receptors by endogenous IgE^7,8. These findings gave rise to two related ideas: first, that it might be possible to ameliorate allergic diseases by passively administering, or by actively stimulating the production of a large amount of ‘irrelevant’ IgE; and second, that a high parasite-induced IgE level might protect against unrelated allergies by means of competition for mast cell receptors^6,7,9. However, searches for epidemiological evidence of such a protective effect have had conflicting results^10–21. We have examined this question using egg-albumin (E A)-hypersensitive rats infected with Nippostrongylus brasiliensis and now show that ‘nonspecific’ IgE induced by helminth infection, although having the capacity to block passive sensitisation, does not inhibit hypersensitivity reactions mediated by an actively produced IgE antibody.