Allergic reactions can be considered as maladaptive
IgE immune responses towards environmental
antigens. Intriguingly, these mechanisms are observed to be very similar to those implicated in the acquisition of an important degree of immunity against metazoan parasites (helminths and arthropods) in mammalian hosts. Based on the hypothesis that
IgE-mediated immune responses evolved in mammals to provide extra protection against metazoan parasites rather than to cause
allergy, we predict that the environmental
allergens will share key properties with the metazoan parasite
antigens that are specifically targeted by
IgE in infected human populations. We seek to test this prediction by examining if significant similarity exists between molecular features of
allergens and
helminth proteins that induce an
IgE response in the human host. By employing various computational approaches, 2712 unique
protein molecules that are known
IgE antigens were searched against a dataset of
proteins from helminths and parasitic arthropods, resulting in a comprehensive list of 2445 parasite
proteins that show significant similarity through sequence and structure with allergenic
proteins. Nearly half of these parasite
proteins from 31 species fall within the 10 most abundant allergenic protein domain families (EF-hand,
Tropomyosin, CAP,
Profilin,
Lipocalin,
Trypsin-like serine protease, Cupin, BetV1, Expansin and
Prolamin). We identified
epitopic-like regions in 206 parasite
proteins and present the first example of a
plant protein (BetV1) that is the commonest
allergen in pollen in a worm, and confirming it as the target of
IgE in
schistosomiasis infected humans. The identification of significant similarity, inclusive of the
epitopic regions, between
allergens and
helminth proteins against which
IgE is an observed marker of protective immunity explains the 'off-target' effects of the
IgE-mediated immune system in
allergy. All these findings can impact the discovery and design of molecules used in
immunotherapy of allergic conditions.