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Structural and immunologic cross-reactivity among filarial and mite tropomyosin: Implications for the hygiene hypothesis - 10/08/11

Doi : 10.1016/j.jaci.2010.11.007 
Helton C. Santiago, MD, PhD a, Sasisekhar Bennuru, PhD a, Alexis Boyd, MSc a, b, Mark Eberhard, PhD c, Thomas B. Nutman, MD a, ⁎
a Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Md 
b George Washington University, Washington, DC 
c Division of Parasitic Diseases, Centers for Disease Control and Prevention, Atlanta, Ga 

Reprint requests: Thomas B. Nutman, MD, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, 4 Center Drive, Building 4, Room B105, NIH, Bethesda, MD 20892-0415.

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.

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Key words : Allergy, antibody cross-reactivity, Dermatophagoides pteronyssinus, filariasis, hygiene hypothesis, tropomyosin

Abbreviations used : BMA, Fil+, Fil–, Fil-A, Fil-NA, GM, GST, HDM, Ni-A, Ni-NA, OR, OvTrop, RR


Mappa


 Supported by the Intramural Research Program, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health.
 Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest.


© 2010  Pubblicato da Elsevier Masson SAS.
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Vol 127 - N° 2

P. 479-486 - febbraio 2011 Ritorno al numero
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