Amb a 1 isoforms: Unequal siblings with distinct immunological features

被引:28
作者
Wolf, M. [1 ]
Twaroch, T. E. [2 ]
Huber, S. [1 ]
Reithofer, M. [3 ]
Steiner, M. [1 ,4 ]
Aglas, L. [1 ]
Hauser, M. [1 ]
Aloisi, I. [5 ]
Asam, C. [1 ]
Hofer, H. [1 ]
Parigiani, M. A. [1 ]
Ebner, C. [6 ]
Bohle, B. [3 ]
Briza, P. [1 ]
Neubauer, A. [2 ]
Stolz, F. [2 ]
Jahn-Schmid, B. [3 ]
Wallner, M. [1 ]
Ferreira, F. [1 ]
机构
[1] Univ Salzburg, Dept Mol Biol, Salzburg, Austria
[2] Biomay AG, Vienna Competence Ctr, Vienna, Austria
[3] Med Univ Vienna, Dept Pathophysiol & Allergy Res, Vienna, Austria
[4] Paracelsus Med Univ, Lab Immunol & Mol Canc Res, Salzburg, Austria
[5] Univ Bologna, Dept Biol Geol & Environm Sci, Bologna, Italy
[6] Allergy Clin Reumannplatz, Vienna, Austria
基金
奥地利科学基金会;
关键词
allergenicity; Amb a 1 allergen; cross-reactivity; immunogenicity; ragweed pollen allergy; BINDING FAB ASSAY; RAGWEED ANTIGEN-E; IMMUNOGLOBULIN G4; POLLEN ALLERGEN; ANTIBODY; IMMUNOTHERAPY; SENSITIZATION; EXPOSURE; MULTICENTER; PREVALENCE;
D O I
10.1111/all.13196
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
BackgroundRagweed pollen represents a major allergy risk factor. Ragweed extracts contain five different isoforms of the major allergen Amb a 1. However, the immunological characteristics of Amb a 1 isoforms are not fully investigated. Here, we compared the physicochemical and immunological properties of three most important Amb a 1 isoforms. MethodsAfter purification, the isoforms were physicochemically characterized, tested for antibody binding and induction of human T-cell proliferative responses. Their immunological properties were further evaluated in vitro and in vivo in a mouse model. ResultsAmb a 1 isoforms exhibited distinct patterns of IgE binding and immunogenicity. Compared to Amb a 1.02 or 03 isoforms, Amb a 1.01 showed higher IgE-binding activity. Isoforms 01 and 03 were the most potent stimulators of patients' T cells. In a mouse model of immunization, Amb a 1.01 induced higher levels of IgG and IgE antibodies when compared to isoforms 02 and 03. Interestingly, ragweed-sensitized patients also displayed an IgG response to Amb a 1 isoforms. However, unlike therapy-induced antibodies, sensitization-induced IgG did not show IgE-blocking activity. ConclusionThe present study showed that naturally occurring isoforms of Amb a 1 possess different immunogenic and sensitizing properties. These findings should be considered when selecting sequences for molecule-based diagnosis and therapy for ragweed allergy. Due to its high IgE-binding activity, isoform Amb a 1.01 should be included in diagnostic tests. In contrast, due to their limited B- and T-cell cross-reactivity patterns, a combination of different isoforms might be a more attractive strategy for ragweed immunotherapy.
引用
收藏
页码:1874 / 1882
页数:9
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