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

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

<p>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

<p>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

<p>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

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

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