Immunoglobulin-E-mediated reactivity to self antigens: a controversial issue

Immunoglobulin E (IgE) reactivity to self antigens is well established in vitro by ELISA, inhibition ELISA, Western blot analyses and T cell proliferation experiments. In vivo, IgE-binding self antigens are able to elicit strong type I reactions in sensitized individuals and, in the case of human manganese superoxide dismutase, to elicit eczematous reactions on healthy skin areas of patients suffering from atopic eczema. The reactions against self antigens sharing structural homology with environmental allergens can be plausibly explained by molecular mimicry between common B cell epitopes. For the second class of IgE-binding self antigens without sequence homology to known allergens, it is still unclear if the structures are able to induce a B cell switch to IgE production, or if the reactivity is due to sequence similarity shared with not yet detected environmental allergens. However, in all cases, cross-reactivity is never complete, indicating either a lower affinity of IgE antibodies to self allergens than to the homologous environmental allergens or the presence of additional B cell epitopes on the surface of the environmental allergens, or both. Increasing evidence shows that self allergens could play a decisive role in the exacerbation of long-lasting atopic diseases. However, the only observation supporting a clinical role of IgE-mediated autoreactivity is confined to the fact that IgE levels against self antigens correlate with disease severity.