Ablation of ovomucoid-induced allergic response by desensitization with recombinant ovomucoid third domain in a murine model
Notice bibliographique
Résumé
Attempts to modulate the allergenic response by hypoallergens aimed at eliminating IgE-binding epitopes have been established recently for allergen immunotherapy. Desensitization offers an alternative approach to mounting a protective immune response. We have shown previously that mutation of the decisive amino acids in the B cell epitope of the ovomucoid third domain suppresses IgE binding reactivity against human patient sera and we hypothesize that this hypoallergenic variant could be a potential candidate molecule for specific immunotherapy against an ovomucoid-induced IgE reaction. The aim of this study was to investigate whether hyposensitization with the ovomucoid-modified isoform could desensitize ovomucoid-sensitized mice. We mapped the immunodominant B cell epitopes of ovomucoid in Balb/c mice. A hypoallergenic ovomucoid mutant isoform, having ablated allergenicity against patient sera, was used to desensitize ovomucoid-sensitized Balb/c mice by intraperitoneal injection. Female Balb/c mice were sensitized with intact ovomucoid molecule (Fovm) and desensitized with the modified isoform of the third domain of ovomucoid (GMFA). Intact ovomucoid-sensitized mice desensitized with phosphate-buffered saline (PBS) served as positive controls to maintain hypersensitivity. To gain insight into the efficacy of the modified ovomucoid variant in desensitization, effects on hypersensitivity reactions and histamine levels, followed by its association with antibody levels and cytokine profiles, were measured. Abrogation of the allergic response with complete suppression of anaphylactic symptoms and lower serum histamine levels was observed in the desensitized group by GMFA, accompanied by significantly reduced ovomucoid-specific IgE and IgG1 levels and enhanced specific IgG and IgG2a levels. The sensitized group showed severe anaphylactic symptoms, enhanced serum histamine concentrations and increased levels of specific IgE and IgG1. The level of interleukin (IL)-4 was decreased dramatically in the desensitized group and higher levels of interferon (IFN)-gamma were found, whereas mice sensitized with intact ovomucoid exhibited significantly higher levels of IL-4 favouring a Th2 skewed pathway. We demonstrate clearly that GMFA is able to ablate ovomucoid-induced allergic reactions in sensitized mice. This occurs via a suppression of specific IgE accompanied by an increase in suppressor T cell activity. This approach offers some promise for the development of treatment against ovomucoid-induced allergic response.
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».