Structural and immunologic cross-reactivity among filarial and mite tropomyosin: implications for the hygiene hypothesis

J Allergy Clin Immunol. 2011 Feb;127(2):479-86. doi: 10.1016/j.jaci.2010.11.007. Epub 2010 Dec 24.

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.

Conclusion: Filarial infection induces strong cross-reactive antitropomyosin antibody responses that may affect sensitization and regulation of allergic reactivity.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Antigens, Dermatophagoides
  • Antigens, Plant / immunology*
  • Arthropod Proteins
  • Cross Reactions
  • Filariasis / immunology
  • Humans
  • Hygiene*
  • Hypersensitivity / etiology*
  • Immunoglobulin E / blood
  • Immunoglobulin G / blood
  • Onchocerca volvulus / immunology*
  • Tropomyosin / chemistry
  • Tropomyosin / immunology*

Substances

  • Antigens, Dermatophagoides
  • Antigens, Plant
  • Arthropod Proteins
  • Immunoglobulin G
  • Tropomyosin
  • der p 10 protein, Dermatophagoides pteronyssinus
  • Immunoglobulin E