Known allergen structures predict Schistosoma mansoni IgE-binding antigens in human infection

Farnell, Edward J., Tyagi, Nidhi, Ryan, Stephanie, Chalmers, Iain W., Pinot de Moira, Angela, Jones, Frances M., Wawrzyniak, Jakub, Fitzsimmons, Colin M., Tukahebwa, Edridah M., Furnham, Nicholas, Maizels, Rick M., and Dunne, David W. (2015) Known allergen structures predict Schistosoma mansoni IgE-binding antigens in human infection. Frontiers in Immunology, 6. 26. pp. 1-14.

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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.

Item ID: 38083
Item Type: Article (Research - C1)
ISSN: 1664-3224
Keywords: schistosomiasis mansoni, allergenicity, IgE, IgG4, parasite allergens, metazoan parasite, helminth proteins
Additional Information:

© 2015 Farnell, Tyagi, Ryan, Chalmers, Pinot de Moira, Jones, Wawrzyniak, Fitzsimmons, Tukahebwa, Furnham, Maizels and Dunne. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Funders: Welcome Trust (WT), European Commission (EC)
Projects and Grants: WT program 083931/Z/07/Z, WT project 094317/Z/10/Z, EC FP7-CP-IP-SICA scheme grant 242107
Date Deposited: 03 Jul 2015 01:40
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1108 Medical Microbiology > 110803 Medical Parasitology @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 100%
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