Abstract
The IgE response has been associated with both allergic reactions and immunity to metazoan parasites. Recently, we hypothesized that all environmental allergens bear structural homology to IgE-binding antigens from metazoan parasites and that this homology defines the relatively small number of protein families containing allergenic targets. In this study, known allergen structures (Pfam domains) from major environmental allergen families were used to predict allergen-like (SmProfilin, SmVAL-6, SmLipocalin, SmHSP20, Sm triosephosphate isomerase, SmThioredoxin, Sm superoxide dismutase, SmCyclophilin, and Sm phosphoglycerate kinase) and non-allergen-like [Sm dynein light chain (SmDLC), SmAldolase SmAK, SmUbiquitin, and Sm14-3-3] proteins in Schistosoma mansoni. Recombinant antigens were produced in Escherichia coli and IgG1, IgG4, and IgE responses against them measured in a cohort of people (n = 222) infected with S. mansoni. All allergen-like antigens were targeted by IgE responses in infected subjects, whilst IgE responses to the non-allergen-like antigens, SmAK, SmUbiquitin, and Sm14-3-3 were essentially absent being of both low prevalence and magnitude. Two new IgE-binding Pfam domain families, not previously described in allergen family databases, were also found, with prevalent IgE responses against SmDLC (PF01221) and SmAldolase (PF00274). Finally, it was demonstrated that immunoregulatory serological processes typically associated with allergens also occurred in responses to allergen-like proteins in S. mansoni infections, including the production of IgG4 in people responding with IgE and the down-regulation of IgE in response to increased antigen exposure from S. mansoni eggs. This study establishes that structures of known allergens can be used to predict IgE responses against homologous parasite allergen-like molecules (parallergens) and that serological responses with IgE/IgG4 to parallergens mirror those seen against allergens, supporting our hypothesis that allergenicity is rooted in expression of certain protein domain families in metazoan parasites.
Highlights
The role of IgE in allergic immune responses is well established and extensive research has characterized ≈3000 known allergens [1, 2]
We searched for potential parallergens amongst the 32 S. mansoni proteins that were identified in the proteomic study of Curwen et al [21] as being abundant in lifecycle stages found in the human host
Allergy and atopic spectrum diseases have been extensively studied over a number of decades providing a detailed description of many of the protein allergens that are associated with IgE-mediated allergic immune reactions [1, 3]
Summary
The role of IgE in allergic immune responses is well established and extensive research has characterized ≈3000 known allergens [1, 2]. Just 10 Pfam protein domains represent no fewer than 40% of the 995 molecular protein allergens described in the Allfam allergen family database. Many different biochemical properties of proteins have been suggested to be determinants of allergenicity including size, solubility, hydrophobicity, protein fold stability, oligermerization, venom toxicity, post-translational modifications, and protease activity [2, 4]. None of these factors independently describe all allergens or differentiate satisfactorily between allergens and non-allergens, for example, not all allergens are proteases and there are many examples of non-allergenic proteases
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