Abstract
Helminth infections and allergy have evolutionary and clinical links. Infection with the nematode Ascaris lumbricoides induces IgE against several molecules including invertebrate pan-allergens. These antibodies influence the pathogenesis and diagnosis of allergy; therefore, studying parasitic and non-parasitic allergens is essential to understand both helminth immunity and allergy. Glutathione transferases (GSTs) from cockroach and house dust mites are clinically relevant allergens and comparative studies between them and the GST from A. lumbricoides (GSTA) are necessary to evaluate their allergenicity. We sought to analyze the allergenic potential of GSTA in connection with the IgE response to non-parasitic GSTs. IgE to purified GSTs from Ascaris (nGSTA and rGSTA), house dust mites (rDer p 8, nBlo t 8 and rBlo t 8), and cockroach (rBla g 5) was measured by ELISA in subjects from Cartagena, Colombia. Also, multidimensional proteomic approaches were used to study the extract of A. lumbricoides and investigate the existence of GST isoforms. We found that among asthmatics, the strength of IgE levels to GSTA was significantly higher than to mite and cockroach GSTs, and there was a strong positive correlation between IgE levels to these molecules.Specific IgE to GSTA was found in 13.2% of controls and 19.5% of asthmatics. In addition nGSTA induced wheal and flare in skin of sensitized asthmatics indicating that it might be of clinical relevance for some patients. Frequency and IgE levels to GSTA were higher in childhood and declined with age. At least six GST isoforms in A. lumbricoides bind human IgE. Four isoforms were the most abundant and several amino acid substitutions were found, mainly on the N-terminal domain. In conclusion, a new allergenic component of Ascaris has been discovered; it could have clinical impact in allergic patients and influence the diagnosis of mite and cockroach allergy in tropical environments.
Highlights
Allergic diseases such as asthma are public health problems and, together with other immune mediated diseases, are increasing worldwide [1]
To further analyze this component, the A. lumbricoides extract was separated by Ion-Pair Reverse-Phased micro High Performance Liquid Chromatography (IP-RP-mHPLC) and each fraction was analyzed by mass spectrometry
We identified a group of asthmatic patients that were sensitized, to GST from A. lumbricoides (GSTA) and to mite GSTs (Der p 8 and Blo t 8), suggesting that this allergenic group might be of clinical relevance for some patients living in the tropics (Figure 2E & file S1)
Summary
Allergic diseases such as asthma are public health problems and, together with other immune mediated diseases, are increasing worldwide [1]. There is cross reactivity among several IgE-binding components of Ascaris and other invertebrates such as domestic mites [5,6,7] and cockroaches [8] Because of their potential impact on protective immunity to Ascaris and the pathogenesis and diagnosis of allergic diseases (e.g. asthma), the characterization of immunogenic and allergenic components of Ascaris is essential. Two allergens from this nematode have been described (Asc s 1 and Asc l 3) and we have evidence that the glutathione transferase of Ascaris suum binds IgE [8]. There is evidence suggesting that they exist as isoforms in cockroach, house dust mites and nematodes [12,19,20]
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