Blocking antibodies induced by immunization with a hypoallergenic parvalbumin mutant reduce allergic symptoms in a mouse model of fish allergy - 27/09/17
Abstract |
Background |
Fish is a frequent elicitor of severe IgE-mediated allergic reactions. Beside avoidance, there is currently no allergen-specific therapy available. Hypoallergenic variants of the major fish allergen, parvalbumin, for specific immunotherapy based on mutation of the 2 calcium-binding sites have been developed.
Objectives |
This study sought to establish a mouse model of fish allergy resembling human disease and to investigate whether mouse and rabbit IgG antibodies induced by immunization with a hypoallergenic mutant of the major carp allergen protect against allergic symptoms in sensitized mice.
Methods |
C3H/HeJ mice were sensitized with recombinant wildtype Cyp c 1 or carp extract by intragastric gavage. Antibody, cellular immune responses, and epitope specificity in sensitized mice were investigated by ELISA, rat basophil leukemia assay, T-cell proliferation experiments using recombinant wildtype Cyp c 1, and overlapping peptides spanning the Cyp c 1 sequence. Anti-hypoallergenic Cyp c 1 mutant mouse and rabbit sera were tested for their ability to inhibit IgE recognition of Cyp c 1, Cyp c 1–specific basophil degranulation, and Cyp c 1–induced allergic symptoms in the mouse model.
Results |
A mouse model of fish allergy mimicking human disease regarding IgE epitope recognition and symptoms as close as possible was established. Administration of antisera generated in mice and rabbits by immunization with a hypoallergenic Cyp c 1 mutant inhibited IgE binding to Cyp c 1, Cyp c 1–induced basophil degranulation, and allergic symptoms caused by allergen challenge in sensitized mice.
Conclusions |
Antibodies induced by immunization with a hypoallergenic Cyp c 1 mutant protect against allergic reactions in a murine model of fish allergy.
Le texte complet de cet article est disponible en PDF.Key words : Blocking antibodies, fish allergy, hypoallergenic parvalbumin mutant, specific immunotherapy
Abbreviations used : ELISA, hP62, HRP, i.p., mCyp c 1, OD, RBL, rCyp c 1, rPhl p 1, SIT
Plan
| Supported by the FAST (Food Allergy Specific Immunotherapy) project 201871 of the Seventh Framework Program for Research of the European Union and by the Austrian Science Fund, Projects P23350-B11 and F4605. |
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| Disclosure of potential conflict of interest: A. Gstoettner has received travel support from FAST Project of the European Union and is employed by Sandoz. R. van Ree's institution has received a grant from the European Commission. R. Valenta has received research support from Biomay AG, Vienna, Austria, Thermofisher, Uppsala, Sweden, and Fresenius Medical Care, Bad Homburg, Germany, and serves as consultant for these companies. B. Linhart has received research support from the FAST Project201871 of the European Union and the Austrian Science Fund. The rest of the authors declare they have no relevant conflicts of interest. |
Vol 139 - N° 6
P. 1897 - juin 2017 Retour au numéro
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