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Molecular mimicry between cockroach and helminth glutathione S-transferases promotes crossreactivity and cross-sensitization

Identifieur interne : 004106 ( Main/Exploration ); précédent : 004105; suivant : 004107

Molecular mimicry between cockroach and helminth glutathione S-transferases promotes crossreactivity and cross-sensitization

Auteurs : Helton Santiago [États-Unis] ; Elyse Leevan [États-Unis] ; Sasisekhar Bennuru [États-Unis] ; Flavia Ribeiro-Gomes [États-Unis] ; Ellen Mueller [États-Unis] ; Mark Wilson [États-Unis] ; Thomas Wynn [États-Unis] ; David Garboczi [États-Unis] ; Joseph Urban [États-Unis] ; Edward Mitre [États-Unis] ; Thomas B. Nutman

Source :

RBID : PMC:3387355

Descripteurs français

English descriptors

Abstract

Background

The extensive similarities between helminth proteins and allergens are thought to contribute to helminth-driven allergic sensitization.

Objective

To investigate the cross-reactivity between a major glutathione-S transferase (GST) allergen of cockroach (Bla g 5) and the GST of Wuchereria bancrofti (WbGST), a major lymphatic filarial pathogen of humans.

Methods

We compared the molecular and structural similarities between Bla g 5 and WbGST by in silico analysis and by linear epitope mapping. Levels of IgE, IgG and IgG4 antibodies were measured in filarial-infected and –uninfected patients. Mice were infected with Heligmosomoides bakeri (Hb) and skin tested for cross-reactive allergic responses.

Results

These two proteins are 30% identical at the amino acid level with remarkable similarity in the N-terminal region and overall structural conservation based on predicted three-dimensional models. Filarial infection was associated with IgE, IgG, and IgG4 anti-Bla g 5 Ab production, with a significant correlation between Abs (irrespective of isotype) to Bla g 5 and WbGST (P < 0.0003). Pre-incubation of sera from cockroach allergic subjects with WbGST partially depleted (by 50 to 70%) anti-Bla g 5 IgE, IgG, and IgG4 Abs. IgE epitope mapping of Bla g 5 revealed that two linear N-terminal epitopes are highly conserved in WbGST corresponding to Bla g 5 peptides partially involved in the inhibition of WbGST binding. Finally, mice infected with Hb developed anti-HbGST IgE and showed immediate type skin test reactivity to Bla g 5.

Conclusion

These data demonstrate that helminth GST and the aeroallergen Bla g 5 share epitopes that can induce allergic cross-sensitization.


Url:
DOI: 10.1016/j.jaci.2012.02.045
PubMed: 22541242
PubMed Central: 3387355


Affiliations:


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Le document en format XML

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<name sortKey="Wilson, Mark" sort="Wilson, Mark" uniqKey="Wilson M" first="Mark" last="Wilson">Mark Wilson</name>
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<name sortKey="Wynn, Thomas" sort="Wynn, Thomas" uniqKey="Wynn T" first="Thomas" last="Wynn">Thomas Wynn</name>
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<nlm:aff id="A1">The Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
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<name sortKey="Garboczi, David" sort="Garboczi, David" uniqKey="Garboczi D" first="David" last="Garboczi">David Garboczi</name>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland</wicri:regionArea>
<placeName>
<region type="state">Maryland</region>
</placeName>
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<name sortKey="Urban, Joseph" sort="Urban, Joseph" uniqKey="Urban J" first="Joseph" last="Urban">Joseph Urban</name>
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<nlm:aff id="A4">Diet, Genomics, and Immunology Laboratory, Beltsville Human Nutrition Research Center, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, Maryland, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Diet, Genomics, and Immunology Laboratory, Beltsville Human Nutrition Research Center, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, Maryland</wicri:regionArea>
<placeName>
<region type="state">Maryland</region>
</placeName>
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<name sortKey="Mitre, Edward" sort="Mitre, Edward" uniqKey="Mitre E" first="Edward" last="Mitre">Edward Mitre</name>
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<nlm:aff id="A2">Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA</nlm:aff>
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<keywords scheme="KwdEn" xml:lang="en">
<term>Amino Acid Sequence</term>
<term>Animals</term>
<term>Antibodies (blood)</term>
<term>Cockroaches (enzymology)</term>
<term>Cockroaches (genetics)</term>
<term>Cockroaches (immunology)</term>
<term>Cross Reactions</term>
<term>Elephantiasis, Filarial (immunology)</term>
<term>Epitope Mapping</term>
<term>Female</term>
<term>Glutathione Transferase (chemistry)</term>
<term>Glutathione Transferase (genetics)</term>
<term>Glutathione Transferase (immunology)</term>
<term>Helminth Proteins (chemistry)</term>
<term>Helminth Proteins (genetics)</term>
<term>Helminth Proteins (immunology)</term>
<term>Helminths (enzymology)</term>
<term>Helminths (immunology)</term>
<term>Humans</term>
<term>Immunoglobulin E (blood)</term>
<term>Immunoglobulin E (immunology)</term>
<term>Insect Proteins (chemistry)</term>
<term>Insect Proteins (genetics)</term>
<term>Insect Proteins (immunology)</term>
<term>Mice</term>
<term>Mice, Inbred BALB C</term>
<term>Models, Molecular</term>
<term>Molecular Mimicry (immunology)</term>
<term>Molecular Sequence Data</term>
<term>Phylogeny</term>
<term>Sequence Analysis, DNA</term>
<term>Trichostrongyloidea (immunology)</term>
<term>Trichostrongyloidiasis (immunology)</term>
<term>Wuchereria bancrofti (enzymology)</term>
<term>Wuchereria bancrofti (genetics)</term>
<term>Wuchereria bancrofti (immunology)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr">
<term>Analyse de séquence d'ADN</term>
<term>Animaux</term>
<term>Anticorps (sang)</term>
<term>Blattes (enzymologie)</term>
<term>Blattes (génétique)</term>
<term>Blattes (immunologie)</term>
<term>Cartographie épitopique</term>
<term>Données de séquences moléculaires</term>
<term>Femelle</term>
<term>Filariose lymphatique (immunologie)</term>
<term>Glutathione transferase ()</term>
<term>Glutathione transferase (génétique)</term>
<term>Glutathione transferase (immunologie)</term>
<term>Helminthes (enzymologie)</term>
<term>Helminthes (immunologie)</term>
<term>Humains</term>
<term>Immunoglobuline E (immunologie)</term>
<term>Immunoglobuline E (sang)</term>
<term>Infections à Trichostrongyloidea (immunologie)</term>
<term>Mimétisme moléculaire (immunologie)</term>
<term>Modèles moléculaires</term>
<term>Phylogénie</term>
<term>Protéines d'helminthes ()</term>
<term>Protéines d'helminthes (génétique)</term>
<term>Protéines d'helminthes (immunologie)</term>
<term>Protéines d'insecte ()</term>
<term>Protéines d'insecte (génétique)</term>
<term>Protéines d'insecte (immunologie)</term>
<term>Réactions croisées</term>
<term>Souris</term>
<term>Souris de lignée BALB C</term>
<term>Séquence d'acides aminés</term>
<term>Trichostrongyloidea (immunologie)</term>
<term>Wuchereria bancrofti (enzymologie)</term>
<term>Wuchereria bancrofti (génétique)</term>
<term>Wuchereria bancrofti (immunologie)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en">
<term>Antibodies</term>
<term>Immunoglobulin E</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en">
<term>Glutathione Transferase</term>
<term>Helminth Proteins</term>
<term>Insect Proteins</term>
</keywords>
<keywords scheme="MESH" qualifier="enzymologie" xml:lang="fr">
<term>Blattes</term>
<term>Helminthes</term>
<term>Wuchereria bancrofti</term>
</keywords>
<keywords scheme="MESH" qualifier="enzymology" xml:lang="en">
<term>Cockroaches</term>
<term>Helminths</term>
<term>Wuchereria bancrofti</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en">
<term>Cockroaches</term>
<term>Glutathione Transferase</term>
<term>Helminth Proteins</term>
<term>Insect Proteins</term>
<term>Wuchereria bancrofti</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr">
<term>Blattes</term>
<term>Glutathione transferase</term>
<term>Protéines d'helminthes</term>
<term>Protéines d'insecte</term>
<term>Wuchereria bancrofti</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr">
<term>Blattes</term>
<term>Filariose lymphatique</term>
<term>Glutathione transferase</term>
<term>Helminthes</term>
<term>Immunoglobuline E</term>
<term>Infections à Trichostrongyloidea</term>
<term>Mimétisme moléculaire</term>
<term>Protéines d'helminthes</term>
<term>Protéines d'insecte</term>
<term>Trichostrongyloidea</term>
<term>Wuchereria bancrofti</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en">
<term>Cockroaches</term>
<term>Elephantiasis, Filarial</term>
<term>Glutathione Transferase</term>
<term>Helminth Proteins</term>
<term>Helminths</term>
<term>Immunoglobulin E</term>
<term>Insect Proteins</term>
<term>Molecular Mimicry</term>
<term>Trichostrongyloidea</term>
<term>Trichostrongyloidiasis</term>
<term>Wuchereria bancrofti</term>
</keywords>
<keywords scheme="MESH" qualifier="sang" xml:lang="fr">
<term>Anticorps</term>
<term>Immunoglobuline E</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Amino Acid Sequence</term>
<term>Animals</term>
<term>Cross Reactions</term>
<term>Epitope Mapping</term>
<term>Female</term>
<term>Humans</term>
<term>Mice</term>
<term>Mice, Inbred BALB C</term>
<term>Models, Molecular</term>
<term>Molecular Sequence Data</term>
<term>Phylogeny</term>
<term>Sequence Analysis, DNA</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>Analyse de séquence d'ADN</term>
<term>Animaux</term>
<term>Cartographie épitopique</term>
<term>Données de séquences moléculaires</term>
<term>Femelle</term>
<term>Glutathione transferase</term>
<term>Humains</term>
<term>Modèles moléculaires</term>
<term>Phylogénie</term>
<term>Protéines d'helminthes</term>
<term>Protéines d'insecte</term>
<term>Réactions croisées</term>
<term>Souris</term>
<term>Souris de lignée BALB C</term>
<term>Séquence d'acides aminés</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<sec id="S1">
<title>Background</title>
<p id="P2">The extensive similarities between helminth proteins and allergens are thought to contribute to helminth-driven allergic sensitization.</p>
</sec>
<sec id="S2">
<title>Objective</title>
<p id="P3">To investigate the cross-reactivity between a major glutathione-S transferase (GST) allergen of cockroach (Bla g 5) and the GST of
<italic>Wuchereria bancrofti</italic>
(WbGST), a major lymphatic filarial pathogen of humans.</p>
</sec>
<sec id="S3">
<title>Methods</title>
<p id="P4">We compared the molecular and structural similarities between Bla g 5 and WbGST by in silico analysis and by linear epitope mapping. Levels of IgE, IgG and IgG4 antibodies were measured in filarial-infected and –uninfected patients. Mice were infected with
<italic>Heligmosomoides bakeri</italic>
(Hb) and skin tested for cross-reactive allergic responses.</p>
</sec>
<sec id="S4">
<title>Results</title>
<p id="P5">These two proteins are 30% identical at the amino acid level with remarkable similarity in the N-terminal region and overall structural conservation based on predicted three-dimensional models. Filarial infection was associated with IgE, IgG, and IgG4 anti-Bla g 5 Ab production, with a significant correlation between Abs (irrespective of isotype) to Bla g 5 and WbGST (
<italic>P</italic>
< 0.0003). Pre-incubation of sera from cockroach allergic subjects with WbGST partially depleted (by 50 to 70%) anti-Bla g 5 IgE, IgG, and IgG4 Abs. IgE epitope mapping of Bla g 5 revealed that two linear N-terminal epitopes are highly conserved in WbGST corresponding to Bla g 5 peptides partially involved in the inhibition of WbGST binding. Finally, mice infected with
<italic>Hb</italic>
developed anti-HbGST IgE and showed immediate type skin test reactivity to Bla g 5.</p>
</sec>
<sec id="S5">
<title>Conclusion</title>
<p id="P6">These data demonstrate that helminth GST and the aeroallergen Bla g 5 share epitopes that can induce allergic cross-sensitization.</p>
</sec>
</div>
</front>
</TEI>
<affiliations>
<list>
<country>
<li>États-Unis</li>
</country>
<region>
<li>Maryland</li>
</region>
</list>
<tree>
<noCountry>
<name sortKey="Nutman, Thomas B" sort="Nutman, Thomas B" uniqKey="Nutman T" first="Thomas B." last="Nutman">Thomas B. Nutman</name>
</noCountry>
<country name="États-Unis">
<region name="Maryland">
<name sortKey="Santiago, Helton" sort="Santiago, Helton" uniqKey="Santiago H" first="Helton" last="Santiago">Helton Santiago</name>
</region>
<name sortKey="Bennuru, Sasisekhar" sort="Bennuru, Sasisekhar" uniqKey="Bennuru S" first="Sasisekhar" last="Bennuru">Sasisekhar Bennuru</name>
<name sortKey="Garboczi, David" sort="Garboczi, David" uniqKey="Garboczi D" first="David" last="Garboczi">David Garboczi</name>
<name sortKey="Leevan, Elyse" sort="Leevan, Elyse" uniqKey="Leevan E" first="Elyse" last="Leevan">Elyse Leevan</name>
<name sortKey="Mitre, Edward" sort="Mitre, Edward" uniqKey="Mitre E" first="Edward" last="Mitre">Edward Mitre</name>
<name sortKey="Mueller, Ellen" sort="Mueller, Ellen" uniqKey="Mueller E" first="Ellen" last="Mueller">Ellen Mueller</name>
<name sortKey="Ribeiro Gomes, Flavia" sort="Ribeiro Gomes, Flavia" uniqKey="Ribeiro Gomes F" first="Flavia" last="Ribeiro-Gomes">Flavia Ribeiro-Gomes</name>
<name sortKey="Urban, Joseph" sort="Urban, Joseph" uniqKey="Urban J" first="Joseph" last="Urban">Joseph Urban</name>
<name sortKey="Wilson, Mark" sort="Wilson, Mark" uniqKey="Wilson M" first="Mark" last="Wilson">Mark Wilson</name>
<name sortKey="Wynn, Thomas" sort="Wynn, Thomas" uniqKey="Wynn T" first="Thomas" last="Wynn">Thomas Wynn</name>
</country>
</tree>
</affiliations>
</record>

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