Molecular mimicry between cockroach and helminth glutathione S-transferases promotes crossreactivity and cross-sensitization
Identifieur interne : 003634 ( Pmc/Corpus ); précédent : 003633; suivant : 003635Molecular mimicry between cockroach and helminth glutathione S-transferases promotes crossreactivity and cross-sensitization
Auteurs : Helton Santiago ; Elyse Leevan ; Sasisekhar Bennuru ; Flavia Ribeiro-Gomes ; Ellen Mueller ; Mark Wilson ; Thomas Wynn ; David Garboczi ; Joseph Urban ; Edward Mitre ; Thomas B. NutmanSource :
- The Journal of Allergy and Clinical Immunology [ 0091-6749 ] ; 2012.
Abstract
The extensive similarities between helminth proteins and allergens are thought to contribute to helminth-driven allergic sensitization.
To investigate the cross-reactivity between a major glutathione-S transferase (GST) allergen of cockroach (Bla g 5) and the GST of
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
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 (
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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PMC:3387355Le document en format XML
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<author><name sortKey="Santiago, Helton" sort="Santiago, Helton" uniqKey="Santiago H" first="Helton" last="Santiago">Helton Santiago</name>
<affiliation><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>
</affiliation>
</author>
<author><name sortKey="Leevan, Elyse" sort="Leevan, Elyse" uniqKey="Leevan E" first="Elyse" last="Leevan">Elyse Leevan</name>
<affiliation><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>
</affiliation>
</author>
<author><name sortKey="Bennuru, Sasisekhar" sort="Bennuru, Sasisekhar" uniqKey="Bennuru S" first="Sasisekhar" last="Bennuru">Sasisekhar Bennuru</name>
<affiliation><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>
</affiliation>
</author>
<author><name sortKey="Ribeiro Gomes, Flavia" sort="Ribeiro Gomes, Flavia" uniqKey="Ribeiro Gomes F" first="Flavia" last="Ribeiro-Gomes">Flavia Ribeiro-Gomes</name>
<affiliation><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>
</affiliation>
</author>
<author><name sortKey="Mueller, Ellen" sort="Mueller, Ellen" uniqKey="Mueller E" first="Ellen" last="Mueller">Ellen Mueller</name>
<affiliation><nlm:aff id="A2">Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wilson, Mark" sort="Wilson, Mark" uniqKey="Wilson M" first="Mark" last="Wilson">Mark Wilson</name>
<affiliation><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>
</affiliation>
</author>
<author><name sortKey="Wynn, Thomas" sort="Wynn, Thomas" uniqKey="Wynn T" first="Thomas" last="Wynn">Thomas Wynn</name>
<affiliation><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>
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<author><name sortKey="Garboczi, David" sort="Garboczi, David" uniqKey="Garboczi D" first="David" last="Garboczi">David Garboczi</name>
<affiliation><nlm:aff id="A3">Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Urban, Joseph" sort="Urban, Joseph" uniqKey="Urban J" first="Joseph" last="Urban">Joseph Urban</name>
<affiliation><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>
</affiliation>
</author>
<author><name sortKey="Mitre, Edward" sort="Mitre, Edward" uniqKey="Mitre E" first="Edward" last="Mitre">Edward Mitre</name>
<affiliation><nlm:aff id="A2">Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA</nlm:aff>
</affiliation>
</author>
<author><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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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Molecular mimicry between cockroach and helminth glutathione S-transferases promotes crossreactivity and cross-sensitization</title>
<author><name sortKey="Santiago, Helton" sort="Santiago, Helton" uniqKey="Santiago H" first="Helton" last="Santiago">Helton Santiago</name>
<affiliation><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>
</affiliation>
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<author><name sortKey="Leevan, Elyse" sort="Leevan, Elyse" uniqKey="Leevan E" first="Elyse" last="Leevan">Elyse Leevan</name>
<affiliation><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>
</affiliation>
</author>
<author><name sortKey="Bennuru, Sasisekhar" sort="Bennuru, Sasisekhar" uniqKey="Bennuru S" first="Sasisekhar" last="Bennuru">Sasisekhar Bennuru</name>
<affiliation><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>
</affiliation>
</author>
<author><name sortKey="Ribeiro Gomes, Flavia" sort="Ribeiro Gomes, Flavia" uniqKey="Ribeiro Gomes F" first="Flavia" last="Ribeiro-Gomes">Flavia Ribeiro-Gomes</name>
<affiliation><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>
</affiliation>
</author>
<author><name sortKey="Mueller, Ellen" sort="Mueller, Ellen" uniqKey="Mueller E" first="Ellen" last="Mueller">Ellen Mueller</name>
<affiliation><nlm:aff id="A2">Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wilson, Mark" sort="Wilson, Mark" uniqKey="Wilson M" first="Mark" last="Wilson">Mark Wilson</name>
<affiliation><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>
</affiliation>
</author>
<author><name sortKey="Wynn, Thomas" sort="Wynn, Thomas" uniqKey="Wynn T" first="Thomas" last="Wynn">Thomas Wynn</name>
<affiliation><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>
</affiliation>
</author>
<author><name sortKey="Garboczi, David" sort="Garboczi, David" uniqKey="Garboczi D" first="David" last="Garboczi">David Garboczi</name>
<affiliation><nlm:aff id="A3">Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Urban, Joseph" sort="Urban, Joseph" uniqKey="Urban J" first="Joseph" last="Urban">Joseph Urban</name>
<affiliation><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>
</affiliation>
</author>
<author><name sortKey="Mitre, Edward" sort="Mitre, Edward" uniqKey="Mitre E" first="Edward" last="Mitre">Edward Mitre</name>
<affiliation><nlm:aff id="A2">Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Nutman, Thomas B" sort="Nutman, Thomas B" uniqKey="Nutman T" first="Thomas B." last="Nutman">Thomas B. Nutman</name>
</author>
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<series><title level="j">The Journal of Allergy and Clinical Immunology</title>
<idno type="ISSN">0091-6749</idno>
<idno type="eISSN">1097-6825</idno>
<imprint><date when="2012">2012</date>
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<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>
<pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">1275002</journal-id>
<journal-id journal-id-type="pubmed-jr-id">4431</journal-id>
<journal-id journal-id-type="nlm-ta">J Allergy Clin Immunol</journal-id>
<journal-id journal-id-type="iso-abbrev">J. Allergy Clin. Immunol.</journal-id>
<journal-title-group><journal-title>The Journal of Allergy and Clinical Immunology</journal-title>
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<issn pub-type="ppub">0091-6749</issn>
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<article-id pub-id-type="doi">10.1016/j.jaci.2012.02.045</article-id>
<article-id pub-id-type="manuscript">NIHMS362688</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><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>
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<kwd>allergy</kwd>
<kwd>hygiene hypothesis</kwd>
<kwd>crossreactivity</kwd>
<kwd>filariasis</kwd>
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<funding-group><award-group><funding-source country="United States">National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID</funding-source>
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</front>
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