Comparison of inflammatory responses to genetically engineered hypoallergenic derivatives of the major birch pollen allergen Bet v 1 and to recombinant Bet v 1 wild type in skin chamber fluids collected from birch pollen–allergic patients - 10/05/12
Abstract |
Background: Nearly 60% of birch pollen–allergic patients react exclusively to Bet v 1. With use of the skin blister model, previously only established for installation of crude allergens, we have for the first time characterized the inflammatory response in vivo to recombinant birch pollen allergen, rBet v 1, molecules (rBet v 1 wild type, fragments and trimer). Objective: Our purpose was to examine whether challenge with rBet v 1 derivatives (fragments and trimer) compared with rBet v 1 wild type differs with respect to influx of activated eosinophils and detectable levels of cytokines/chemokines related to allergic inflammation in skin chambers applied to birch pollen–allergic patients. Methods: The skin blister chambers were filled for 2 hours with rBet v 1, the derivatives or PBS and heparin (negative control). The fluids were analyzed after 2 and 8 hours. The number of eosinophils was determined and EG2 and CD69 expression measured by flow cytometry. Cytokines and mediators were analyzed by ELISA and RIA techniques. Results: Comparable numbers of eosinophils were recruited to the chambers challenged with rBet v 1 molecules, but the eosinophils from the rBet v 1 wild-type challenged chambers showed a significantly higher expression of CD69. The levels of eotaxin were similar in all 4 chambers, whereas rBet v 1 wild type induced significantly higher levels of histamine, eosinophil cationic protein, and GM-CSF than the derivatives did. Recombinant Bet v 1 trimer elicited significantly lower levels of IL-4 compared with rBet v1 wild type. Conclusion: Genetically engineered hypoallergenic rBet v 1 derivatives recruited eosinophils analogously with rBet v 1 wild type. However, the derivatives exhibited a lower capacity to activate eosinophils and to release proinflammatory mediators and T helper type 2–derived cytokines. The derivatives may therefore be candidate molecules for specific immunotherapy of birch pollen allergy with reduced risk of inducing allergenic or inflammatory side effects. (J Allergy Clin Immunol 2000;106:101-9.)
Le texte complet de cet article est disponible en PDF.Keywords : Recombinant birch pollen allergens, rBet v 1, hyopallergenic derivatives, skin blister chambers, eosinophils, CD69, eosinophil cationic protein
Abbreviations : BAL, ECP, EG2, MFI, PBE, r, RAST
Plan
 | Supported by grants from the Swedish Council for Work Life Research, the Swedish Foundation for Health Care Sciences and Allergy Research, the Swedish Asthma and Allergy Association, the Swedish Medical Research Council, the Hesselman Foundation, the Karolinska Institute and the Swedish Society of Medicine, the Interdisciplinary Cooperative Project program of the Austrian Ministry of Research, and by grant No. Y078GEN from the Austrian Science Fund. |
| Reprint requests: Anna Nopp, BSc, Division of Clinical Immunology, Karolinska Hospital, S-171 76 Stockholm, Sweden. |
Vol 106 - N° 1P1
P. 101-109 - juillet 2000 Retour au numéro
Article précédent
- Interaction of fungal spores with the lungs: Distribution and retention of inhaled puffball (Calvatia excipuliformis) spores
- Marianne Geiser, Nicolas Leupin, Isabelle Maye, Vinzenz Im Hof, Peter Gehr
- Monocyte chemoattractant peptide-1 expression during cutaneous allergic reactions in mice is mast cell dependent and largely mediates the monocyte recruitment response
- John R. Gordon
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?