Saturation of immunoglobulin E (IgE) binding sites by polyclonal IgE does not explain the protective effect of helminth infections against atopy.

Helminth infections have been associated with decreased rates of asthma (19, 27) and allergy (4, 13, 14, 22, 30). Among the explanations proposed to explain these findings, the most longstanding is the IgE-blocking hypothesis, which posits that high polyclonal IgE levels induced by helminth infections suppress allergic responses by saturating the high-affinity IgE FcɛRI on basophils and mast cells (5, 11, 14). By preventing sufficient numbers of allergen-specific IgE molecules from binding to these cells, it has been argued that high polyclonal IgE levels inhibit allergen-induced basophil and mast cell degranulation. One of the first studies suggestive of IgE blocking demonstrated that allergen-specific skin test reactivity after intradermal injection of serum containing allergen-specific IgE (the Prausnitz-Kustner test) was inhibited when sera containing high concentrations of non-allergen-specific IgE was first injected into the skin (28). This finding was supported by reports that intradermal sensitization cannot be induced in rats (21) or humans (23) with IgE myeloma and that in vitro sensitization of mast cells from chopped lung fragments is blocked when the tissue is initially incubated with serum from West African subjects with high total IgE levels (6). On the basis of these and other reports, in 1976 the possibility of deliberately infecting allergic patients with parasites for the purpose of inducing high polyclonal IgE antibody levels was suggested (11). Epidemiologic and experimental data obtained since then, however, have provided mixed support for this hypothesis. Of epidemiologic studies that take into account confounding variables, two studies have found a correlation between IgE levels and decreased allergy and asthma (4, 22), whereas two other studies have not (27, 30). Further, while treatment of intestinal geohelminths in Venezuelan children resulted in decreased polyclonal IgE levels, increased allergen skin test reactivity, and increased positivity of Prausnitz-Kustner testing (13), high levels of polyclonal IgE induced by helminth infection did not prevent active sensitization when allergen-specific IgE antibody is produced in vivo in rats (10). Also, unlike IgE myeloma patients, cells from Waorani Indians with high IgE levels can be passively sensitized with sera containing allergen-specific IgE (12). In this study, we sought to determine the validity of the IgE-blocking hypothesis. First we evaluated whether a relationship exists between the ratio of polyclonal IgE to antigen-specific IgE and antigen-driven histamine release in patients with filarial infections that typically induce high polyclonal IgE levels. If large quantities of polyclonal IgE can saturate FcɛRI, then an inverse relationship should exist between polyclonal to antigen-specific IgE ratios and histamine release in response to specific antigen. Second, we sensitized basophils from normal donors with various mixtures of purified human myeloma IgE and filaria patient sera to determine the in vitro ratio of polyclonal to specific IgE necessary to inhibit antigen-specific histamine release. Finally, we studied whether there is a relationship between serum levels of IgE and quantities of IgE bound to basophils. While it is well established that FcɛRI expression on basophils is upregulated in proportion to serum IgE levels in allergic and normal control patients (16, 18), such a relationship has not been substantially confirmed in helminth infections. Evidence that quantities of IgE bound to basophils increase with increasing serum IgE levels in helminth-infected patients suggests that saturation of FcɛRI is not easily achieved in vivo.