Known Allergen Structures Predict Schistosoma mansoni IgE-Binding Antigens in Human Infection.

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dc.creatorFarnell, Edward J
dc.creatorTyagi, Nidhi
dc.creatorRyan, Stephanie
dc.creatorChalmers, Iain W
dc.creatorPinot de Moira, Angela
dc.creatorJones, Frances M
dc.creatorWawrzyniak, Jakub
dc.creatorFitzsimmons, Colin M
dc.creatorTukahebwa, Edridah M
dc.creatorFurnham, Nicholas
dc.creatorMaizels, Rick M
dc.creatorDunne, David W
dc.date2015-03-26T11:09:46Z
dc.date2015-03-26T11:09:46Z
dc.date2015
dc.date.accessioned2026-08-03T02:01:48Z
dc.descriptionThe 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.
dc.descriptionWe would like to thank the people of Namoni Village for their time and co-operation in the study as well as the field workers of the Ugandan Virus Research Institute and the Kenyan Medical Research Institute. Thanks go also to Shona Wilson, Joseph Mwatha, and Timothy Kamau, for their knowledge and skill in collecting and preparing samples for the study. We would also like to thank Maureen Laidlaw of the Schistosomiasis Research Group (University of Cambridge) for her expert technical assistance; Undergraduate students Aws Sadik, Matthew J Murray, Emma Robbins, and Emily Day for their hard work during final year projects in the Schistosomiasis Research Group; and Prof. Dame Janet Thornton at the European Bioinformatics Institute for her continued help and support. This work was supported by the Wellcome Trust via program WT 083931/Z/07/Z and project WT 094317/Z/10/Z grants and by the European Commission via FP7-CP-IP-SICA scheme grant 242107.
dc.descriptionThis is the final published paper. The article was originally published in Frontiers in Immunology 6:26, 03 February 2015, doi: 10.3389/fimmu.2015.00026
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dc.identifierFrontiers in Immunology, 03 February 2015, doi: 10.3389/fimmu.2015.00026
dc.identifier1664-3224
dc.identifierhttps://www.repository.cam.ac.uk/handle/1810/247194
dc.identifier1664-3224
dc.identifier.urihttps://repo.dare.co.zw/handle/123456789/162704
dc.languageEnglish
dc.languageeng
dc.publisherFrontiers
dc.publisherhttps://doi.org/10.3389/fimmu.2015.00026
dc.rightsAttribution 2.0 UK: England & Wales
dc.rightshttps://creativecommons.org/licenses/by/2.0/uk/
dc.subjectIgE
dc.subjectIgG4
dc.subjectallergenicity
dc.subjecthelminth proteins
dc.subjectmetazoan parasite
dc.subjectparasite allergens
dc.subjectschistosomiasis mansoni
dc.titleKnown Allergen Structures Predict Schistosoma mansoni IgE-Binding Antigens in Human Infection.
dc.typeArticle

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