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

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) a...

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Published in:Journal of allergy and clinical immunology 2012-07, Vol.130 (1), p.248-256.e9
Main Authors: Santiago, Helton C., MD, PhD, LeeVan, Elyse, BA, Bennuru, Sasisekhar, PhD, Ribeiro-Gomes, Flavia, PhD, Mueller, Ellen, BA, Wilson, Mark, PhD, Wynn, Thomas, PhD, Garboczi, David, PhD, Urban, Joseph, PhD, Mitre, Edward, MD, Nutman, Thomas B., MD
Format: Article
Language:English
Subjects:
Allergies
allergy
Allergy and Immunology
Amino Acid Sequence
Animals
Antibodies - blood
Biological and medical sciences
cockroach
Cockroaches - enzymology
Cockroaches - genetics
Cockroaches - immunology
Cross Reactions
cross-reactivity
Elephantiasis, Filarial - immunology
Epidemiology. Vaccinations
Epitope Mapping
Female
filariasis
Fundamental and applied biological sciences. Psychology
Fundamental immunology
General aspects
Glutathione Transferase - chemistry
Glutathione Transferase - genetics
Glutathione Transferase - immunology
GST
Helminth Proteins - chemistry
Helminth Proteins - genetics
Helminth Proteins - immunology
Helminths - enzymology
Helminths - immunology
Humans
hygiene hypothesis
Immunoglobulin E - blood
Immunoglobulin E - immunology
Immunopathology
Infections
Infectious diseases
Insect Proteins - chemistry
Insect Proteins - genetics
Insect Proteins - immunology
Medical sciences
Mice
Mice, Inbred BALB C
Models, Molecular
Molecular Mimicry - immunology
Molecular Sequence Data
Parasites
Parasitic diseases
Peptides
Phylogeny
Review boards
Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis
Sequence Analysis, DNA
Trichostrongyloidea - immunology
Trichostrongyloidiasis - immunology
Wuchereria bancrofti - enzymology
Wuchereria bancrofti - genetics
Wuchereria bancrofti - immunology
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Summary: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 IgG4 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 IgG4 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 IgG4 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.
ISSN:0091-6749
1097-6825
DOI:10.1016/j.jaci.2012.02.045