title: Known Allergen Structures Predict Schistosoma mansoni IgE-Binding Antigens in Human Infection.
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.
authors.affiliation: Department of Pathology, University of Cambridge , Cambridge , UK.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Farnell
authors.affiliation: European Bioinformatics Institute , Cambridge , UK.
authors.forename: Nidhi
authors.initials: N
authors.lastname: Tyagi
authors.affiliation: Institute of Immunology and Infection Research, The University of Edinburgh , Edinburgh , UK.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Ryan
authors.affiliation: Institute of Biological, Environmental and Rural Sciences, Aberystwyth University , Aberystwyth , UK.
authors.forename: Iain W
authors.initials: IW
authors.lastname: Chalmers
authors.affiliation: Department of Pathology, University of Cambridge , Cambridge , UK.
authors.forename: Angela
authors.initials: A
authors.lastname: Pinot de Moira
authors.affiliation: Department of Pathology, University of Cambridge , Cambridge , UK.
authors.forename: Frances M
authors.initials: FM
authors.lastname: Jones
authors.affiliation: Department of Pathology, University of Cambridge , Cambridge , UK.
authors.forename: Jakub
authors.initials: J
authors.lastname: Wawrzyniak
authors.affiliation: Department of Pathology, University of Cambridge , Cambridge , UK.
authors.forename: Colin M
authors.initials: CM
authors.lastname: Fitzsimmons
authors.affiliation: Vector Control Division, Ugandan Ministry of Health , Kampala , Uganda.
authors.forename: Edridah M
authors.initials: EM
authors.lastname: Tukahebwa
authors.affiliation: European Bioinformatics Institute , Cambridge , UK ; Department of Pathogen Molecular Biology, London School of Hygiene and Tropical Medicine , London , UK.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Furnham
authors.affiliation: Institute of Immunology and Infection Research, The University of Edinburgh , Edinburgh , UK.
authors.forename: Rick M
authors.initials: RM
authors.lastname: Maizels
authors.affiliation: Department of Pathology, University of Cambridge , Cambridge , UK.
authors.forename: David W
authors.initials: DW
authors.lastname: Dunne
keywords: IgE; IgG4; allergenicity; helminth proteins; metazoan parasite; parasite allergens; schistosomiasis mansoni