title: Structural and immunologic cross-reactivity among filarial and mite tropomyosin: implications for the hygiene hypothesis.
abstract: BACKGROUND
  The hygiene hypothesis suggests that parasitic infection modulates host immune responses and decreases atopy. Other data suggest parasitic infections may induce allergic responsiveness.
  
  
  OBJECTIVE
  To assess the structural and immunologic relationships between the known Dermatophagoides pteronyssinus (Der p 10) tropomyosin allergen and filarial tropomyosin of Onchocerca volvulus (OvTrop).
  
  
  METHODS
  The molecular, structural, and immunologic relationships between OvTrop and Der p 10 were compared. Levels of OvTrop-specific and Der p 10-specific IgE, IgG, and IgG₄ in sera of filaria-infected and filarial-uninfected D pteronyssinus-atopic individuals were compared, as were the responses in nonhuman primates infected with the filarial parasite Loa loa. Cross-reactivity was compared by antigen-mediated depletion assays and functionality by passive basophil sensitization.
  
  
  RESULTS
  Filarial and mite tropomyosins were very similar, with 72% identity at the amino acid level, and overlapping predicted 3-dimensional structures. The prevalence of IgE and IgG to Der p 10 was increased in filaria-infected individuals compared with uninfected subjects. There was a strong correlation between serum levels of Ov- and Der p 10-tropomyosin-specific IgE, IgG, and IgG₄ (P < .0001; r > 0.79). Preincubation of sera from anti-Der p 10-positive subjects with OvTrop completely depleted IgE, IgG, and IgG₄ anti-Der p 10. Basophils sensitized with sera from individuals allergic to Der p 10 released histamine similarly when triggered with OvTrop or Der p 10. Primates experimentally infected with L loa developed IgE that cross-reacted with Der p 10.
  
  
  CONCLUSIONS
  Filarial infection induces strong cross-reactive antitropomyosin antibody responses that may affect sensitization and regulation of allergic reactivity.
authors.affiliation: Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Helton C
authors.initials: HC
authors.lastname: Santiago
authors.forename: Sasisekhar
authors.initials: S
authors.lastname: Bennuru
authors.forename: Alexis
authors.initials: A
authors.lastname: Boyd
authors.forename: Mark
authors.initials: M
authors.lastname: Eberhard
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Nutman
mesh_terms: D000818:Animals; D039741:Antigens, Dermatophagoides; D052179:Antigens, Plant / Q000276:immunology*; D060829:Arthropod Proteins; D003429:Cross Reactions; D005368:Filariasis / Q000276:immunology; D006801:Humans; D006920:Hygiene; D006967:Hypersensitivity / Q000209:etiology*; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D017181:Onchocerca volvulus / Q000276:immunology*; D014335:Tropomyosin / Q000737:chemistry / Q000276:immunology*
chemical_list: D039741:Antigens, Dermatophagoides; D052179:Antigens, Plant; D060829:Arthropod Proteins; D007074:Immunoglobulin G; D014335:Tropomyosin; C111884:der p 10 protein, Dermatophagoides pteronyssinus; D007073:Immunoglobulin E