Epitopes described in "Molecular mimicry between cockroach and helminth glutathione S-transferases promotes cross-reactivity and cross-sensitization."

Article Authors:Helton C Santiago; Elyse LeeVan; Sasisekhar Bennuru; Flavia Ribeiro-Gomes; Ellen Mueller; Mark Wilson; Thomas Wynn; David Garboczi; Joseph Urban; Edward Mitre; Thomas B Nutman
Article Title:Molecular mimicry between cockroach and helminth glutathione S-transferases promotes cross-reactivity and cross-sensitization.
Reference Detail
Reference ID:1024481
Abstract:BACKGROUND: The extensive similarities between helminth proteins and allergens are thought to contribute to helminth-driven allergic sensitization. OBJECTIVE: The objective of this study was to investigate the cross-reactivity between a major glutathione-S transferase allergen of cockroach (Bla g 5) and the glutathione-S transferase 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. The levels of IgE, IgG, and IgG(4) antibodies were measured in filarial-infected and filarial-uninfected patients. Mice were infected with Heligmosomoides bakeri, and their skin was tested for cross-reactive allergic responses. RESULTS: These 2 proteins are 30% identical at the amino acid level with remarkable similarity in the N-terminal region and overall structural conservation based on predicted 3-dimensional models. Filarial infection was associated with IgE, IgG, and IgG(4) anti-Bla g 5 antibody production, with a significant correlation between antibodies (irrespective of isotype) to Bla g 5 and WbGST (P< .0003). Preincubation of sera from cockroach-allergic subjects with WbGST partially depleted (by 50%-70%) anti-Bla g 5 IgE, IgG, and IgG(4) antibodies. IgE epitope mapping of Bla g 5 revealed that 2 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 H bakeri developed anti-HbGST IgE and showed immediate-type skin test reactivity to Bla g 5. CONCLUSION: These data demonstrate that helminth glutathione-S transferase and the aeroallergen Bla g 5 share epitopes that can induce allergic cross-sensitization.
Affiliations:Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. helton.santiago@nih.gov.
Reference Type:Literature
PubMed ID:22541242
Journal:J Allergy Clin Immunol
Journal Volume:130
Article Pages:248-56.e9
Journal ISSN:0091-6749
Article Chemical List:Antibodies;Helminth Proteins;Insect Proteins;Immunoglobulin E;Glutathione Transferase
Article MeSH List:Amino Acid Sequence; Animals; Antibodies(blood); Cockroaches(enzymology; genetics; immunology); Cross Reactions; Elephantiasis, Filarial(immunology); Epitope Mapping; Female; Glutathione Transferase(chemistry; genetics; immunology); Helminth Proteins(chemistry; genetics; immunology); Helminths(enzymology; immunology); Humans; Immunoglobulin E(blood; immunology); Insect Proteins(chemistry; genetics; immunology); Mice; Mice, Inbred BALB C; Models, Molecular; Molecular Mimicry(immunology); Molecular Sequence Data; Phylogeny; Sequence Analysis, DNA; Trichostrongyloidea(immunology); Trichostrongyloidiasis(immunology); Wuchereria bancrofti(enzymology; genetics; immunology)
Curation Last Updated:2015-06-05 03:34:32