title: Molecular mimicry between cockroach and helminth glutathione S-transferases promotes cross-reactivity and cross-sensitization.
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.
  
  
  CONCLUSIONS
  These data demonstrate that helminth glutathione-S transferase and the aeroallergen Bla g 5 share epitopes that can induce allergic cross-sensitization.
authors.affiliation: Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. helton.santiago@nih.gov
authors.forename: Helton C
authors.initials: HC
authors.lastname: Santiago
authors.forename: Elyse
authors.initials: E
authors.lastname: LeeVan
authors.forename: Sasisekhar
authors.initials: S
authors.lastname: Bennuru
authors.forename: Flavia
authors.initials: F
authors.lastname: Ribeiro-Gomes
authors.forename: Ellen
authors.initials: E
authors.lastname: Mueller
authors.forename: Mark
authors.initials: M
authors.lastname: Wilson
authors.forename: Thomas
authors.initials: T
authors.lastname: Wynn
authors.forename: David
authors.initials: D
authors.lastname: Garboczi
authors.forename: Joseph
authors.initials: J
authors.lastname: Urban
authors.forename: Edward
authors.initials: E
authors.lastname: Mitre
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Nutman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000097:blood*; D003058:Cockroaches / Q000201:enzymology* / Q000235:genetics / Q000276:immunology; D003429:Cross Reactions; D004605:Elephantiasis, Filarial / Q000276:immunology; D018604:Epitope Mapping; D005260:Female; D005982:Glutathione Transferase / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D015801:Helminth Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D006376:Helminths / Q000201:enzymology* / Q000276:immunology; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D019476:Insect Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D018716:Molecular Mimicry / Q000276:immunology*; D008969:Molecular Sequence Data; D010802:Phylogeny; D017422:Sequence Analysis, DNA; D014251:Trichostrongyloidea / Q000276:immunology; D014252:Trichostrongyloidiasis / Q000276:immunology; D014958:Wuchereria bancrofti / Q000201:enzymology / Q000235:genetics / Q000276:immunology
chemical_list: D000906:Antibodies; D015801:Helminth Proteins; D019476:Insect Proteins; D007073:Immunoglobulin E; D005982:Glutathione Transferase