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

Identifieur interne : 003633 ( Pmc/Curation ); précédent : 003632; suivant : 003634

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

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

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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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<name sortKey="Wynn, Thomas" sort="Wynn, Thomas" uniqKey="Wynn T" first="Thomas" last="Wynn">Thomas Wynn</name>
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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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<wicri:regionArea>Diet, Genomics, and Immunology Laboratory, Beltsville Human Nutrition Research Center, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, Maryland</wicri:regionArea>
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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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<wicri:regionArea>Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland</wicri:regionArea>
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<name sortKey="Nutman, Thomas B" sort="Nutman, Thomas B" uniqKey="Nutman T" first="Thomas B." last="Nutman">Thomas B. Nutman</name>
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<title level="j">The Journal of Allergy and Clinical Immunology</title>
<idno type="ISSN">0091-6749</idno>
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<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>
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<journal-id journal-id-type="nlm-journal-id">1275002</journal-id>
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<article-title>Molecular mimicry between cockroach and helminth glutathione S-transferases promotes crossreactivity and cross-sensitization</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Santiago</surname>
<given-names>Helton</given-names>
</name>
<degrees>MD, PhD</degrees>
<xref ref-type="aff" rid="A1">a</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>LeeVan</surname>
<given-names>Elyse</given-names>
</name>
<degrees>BA</degrees>
<xref ref-type="aff" rid="A1">a</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Bennuru</surname>
<given-names>Sasisekhar</given-names>
</name>
<degrees>PhD</degrees>
<xref ref-type="aff" rid="A1">a</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Ribeiro-Gomes</surname>
<given-names>Flavia</given-names>
</name>
<degrees>PhD</degrees>
<xref ref-type="aff" rid="A1">a</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Mueller</surname>
<given-names>Ellen</given-names>
</name>
<degrees>BA</degrees>
<xref ref-type="aff" rid="A2">b</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Wilson</surname>
<given-names>Mark</given-names>
</name>
<degrees>PhD</degrees>
<xref ref-type="aff" rid="A1">a</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Wynn</surname>
<given-names>Thomas</given-names>
</name>
<degrees>PhD</degrees>
<xref ref-type="aff" rid="A1">a</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Garboczi</surname>
<given-names>David</given-names>
</name>
<degrees>PhD</degrees>
<xref ref-type="aff" rid="A3">c</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Urban</surname>
<given-names>Joseph</given-names>
</name>
<degrees>PhD</degrees>
<xref ref-type="aff" rid="A4">d</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Mitre</surname>
<given-names>Edward</given-names>
</name>
<degrees>MD</degrees>
<xref ref-type="aff" rid="A2">b</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Nutman</surname>
<given-names>Thomas B.</given-names>
</name>
<degrees>MD</degrees>
</contrib>
</contrib-group>
<aff id="A1">
<label>a</label>
The Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA</aff>
<aff id="A2">
<label>b</label>
Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA</aff>
<aff id="A3">
<label>c</label>
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, USA</aff>
<aff id="A4">
<label>d</label>
Diet, Genomics, and Immunology Laboratory, Beltsville Human Nutrition Research Center, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, Maryland, USA</aff>
<author-notes>
<corresp id="FN1">Reprint requests: Helton Santiago, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, 4 Center Drive, Building 4, Room B1-05, NIH, Bethesda, MD 20892-0415. Telephone: 1-301-451-1889. FAX: 1-301-480-3757.
<email>helton.santiago@nih.gov</email>
</corresp>
<fn id="FN2" fn-type="present-address">
<p>Mark Wilson's present address is: National Institutes for Medical Research, London, England.</p>
</fn>
</author-notes>
<pub-date pub-type="nihms-submitted">
<day>12</day>
<month>3</month>
<year>2012</year>
</pub-date>
<pub-date pub-type="epub">
<day>25</day>
<month>4</month>
<year>2012</year>
</pub-date>
<pub-date pub-type="ppub">
<month>7</month>
<year>2012</year>
</pub-date>
<pub-date pub-type="pmc-release">
<day>01</day>
<month>7</month>
<year>2013</year>
</pub-date>
<volume>130</volume>
<issue>1</issue>
<fpage>248</fpage>
<lpage>256.e9</lpage>
<abstract>
<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>
</abstract>
<kwd-group>
<kwd>GST</kwd>
<kwd>cockroach</kwd>
<kwd>allergy</kwd>
<kwd>hygiene hypothesis</kwd>
<kwd>crossreactivity</kwd>
<kwd>filariasis</kwd>
</kwd-group>
<funding-group>
<award-group>
<funding-source country="United States">National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID</funding-source>
<award-id>Z99 AI999999 || AI</award-id>
</award-group>
<award-group>
<funding-source country="United States">National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID</funding-source>
<award-id>Z01 AI000805-11 || AI</award-id>
</award-group>
</funding-group>
</article-meta>
</front>
</pmc>
</record>

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