Helminth infection alters IgE responses to allergens structurally related to parasite proteins

Abstract

Immunological cross-reactivity between environmental allergens and helminth proteins has been demonstrated, although the clinically related implications of this cross-reactivity have not been addressed. To investigate the impact of molecular similarity among allergens and cross-reactive homologous helminth proteins in IgE-based serologic assessment of allergic disorders in a helminth-infected population, we performed ImmunoCAP tests in filarial-infected and noninfected individuals for IgE measurements to allergen extracts that contained proteins with high levels of homology with helminth proteins as well as IgE against representative recombinant allergens with and without helminth homologs. The impact of helminth infection on the levels and function of the IgE to these specific homologous and nonhomologous allergens was corroborated in an animal model. We found that having a tissue-invasive filarial infection increased the serological prevalence of ImmunoCAP-identified IgE directed against house dust mite and cockroach, but not against timothy grass, the latter with few allergens with homologs in helminth infection. IgE ELISA confirmed that filaria-infected individuals had higher IgE prevalences to those recombinant allergens that had homologs in helminths. Mice infected with the helminth Heligmosomoides polygyrus displayed increased levels of IgE and positive skin tests to allergens with homologs in the parasite. These results show that cross-reactivity among allergens and helminth proteins can have practical implications, altering serologic approaches to allergen testing and bringing a new perspective to the "hygiene hypothesis."

Conflict of interest statement

Disclosure of potential conflict of interest: The authors have declared that they have no conflicts of interest to disclose.

Figures

FIGURE 1

Filarial infection induces high levels of IgE that is potentiated by atopy in infected individuals. Immunocap™ technology was used to assess total (polyclonal) IgE (A) or IgE directed to specific allergen extract in Phadiotop™ positive individuals depicted in Table I (B). Sera are from blood bank donors (Non-Infected, Ni) or filarial-infected patients (Fil+). Individuals were classified as atopic (A) or non-atopic (NA). Each dot represents one individual and the horizontal lines represent the GM. Statistics were performed using Kruskal-Wallis test.

FIGURE 2

Experimental helminth infection can influence allergen-specific IgE. Sera from naïve BALB/c mice (NI) or animals infected twice with the murine helminth Heligmosomoides polygyrus (Hp) and bled 10 days after second infection were used in ELISA assay for for allergen-specific IgE using recombinant allergens from HDM (Der p), cockroach (Bla g) and timothy (Phl p) displaying helminth homologues (A) or not (B). Each dot represents one animal pooled from 3 independent experiments (n=15). Lines represent GM. P was calculated by Mann Whitney test.

FIGURE 3

Experimental helminth infection can induce cross-sensitization to allergens using mouse skin tests. BALB/c animals infected twice with Hp were skin tested ten days after the second infection for allergens with and without homologues in parasites. Ears were injected with 10 µg of recombinant allergen and 1ear thickness was measured at the indicated times with a caliper. Symbols represent mean ± SE of 5 ears per group. Hp and Ni groups differed in their responses to parasite extract (HpE), Der p 1, and Phl p 7 (P< 0.05 by two-way ANOVA). Experiments were performed twice with similar results.