Immunoglobulin-E-Mediated Reactivity to Self Antigens: A Controversial Issue

Abstract

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.

Important research questions in allergy and related diseases: nonallergic rhinitis: a GA2LEN paper

“…Allergy symptoms are usually triggered by an IgE-mediated mechanism, but they can also be elicited by self-antigens (107). Two classes of selfantigens can be involved in allergic reactions: human proteins with extended sequence homology to environmental allergens (108) and self-antigens without any sequence homology to IgE-binding proteins (109).…”

“…Although not yet analysed in detail, some of the cDNA sequences show a high degree of sequence identity and cross-reactivity to environmental allergens (107), as shown by a retrospective analysis of the sequences.…”

Overview of Aspergillus Allergens

“…Of course as for the other allergenic sources not all cloned fungal allergens match to unique structures, because cross-reactivity between homologous structures present in fungal extracts derived from different species is a quite common phenomenon (Table 1). Basically fungal allergens can be subdivided in species-specific allergens which are specific to a species or at least to a genus [11] and phylogenetically highly conserved structures which represent allergens showing cross-reactivity not only with fungal proteins of many fungal species [14,15], but also with homologous proteins of other allergenic sources [16,17], including human proteins [18].…”

“…Interestingly some of these proteins show cross-reactivity also with their homologous human proteins at both, humoral and cellular level. The best investigated structures at this level are human MnSOD [57,58], cyclophilin [30,61] and thioredoxin [29], which were shown to bind to serum IgE from A. fumigatus sensitised patients in vitro, to elicit specific skin test reactions in vivo, and to be potentially involved in the pathogenesis of ABPA and atopic eczema [18,63]. Although the role played by IgE-mediated autoreactivity to self-antigens remains controversial, the fact that the application of human MnSOD in patch test on healthy skin areas of atopic eczema patients sensitised to fungal MnSOD is sufficient to induce an eczematous reaction [57,63] strongly indicates that autoreactivity could contribute to the exacerbation of the symptoms in the absence of external exposure to environmental allergens.…”

“…However, also self-antigens without sequence homology with any known allergen but able to bind serum IgE from atopic eczema patients have been described [64]. For these structures it is still not clear if they are able to directly induce a B cell switch to IgE production, or if the observed IgE-binding capability is due to cross-reactivity with not yet identified environmental allergen structures [18].…”