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

被引:36
作者
Nopp, A [1 ]
Halldén, G
Lundahl, J
Johansson, E
Vrtala, S
Valenta, R
Grönneberg, R
van Hage-Hamsten, M
机构
[1] Karolinska Hosp, Div Clin Immunol, S-17176 Stockholm, Sweden
[2] Huddinge Univ Hosp, Dept Resp Med & Allergol, Stockholm, Sweden
[3] Karolinska Inst, Stockholm, Sweden
[4] Univ Vienna, Vienna Gen Hosp, Mol Immunopathol Grp, Dept Gen & Expt Pathol, Vienna, Austria
基金
奥地利科学基金会;
关键词
recombinant birch pollen allergens; rBet v 1; hyopallergenic derivatives; skin blister chambers; eosinophils; CD69; eosinophil cationic protein;
D O I
10.1067/mai.2000.106924
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
Background: Nearly 60% of birth 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 vl 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 vl molecules, but the eosinophils from the rBet vl 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 vl wild type. Conclusion: Genetically engineered hypoallergenic rBet v 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.
引用
收藏
页码:101 / 109
页数:9
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