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Allergy. 2017 Dec;72(12):1874-1882. doi: 10.1111/all.13196. Epub 2017 Jun 14.

Amb a 1 isoforms: Unequal siblings with distinct immunological features.

Author information

1
Department of Molecular Biology, University of Salzburg, Salzburg, Austria.
2
Biomay AG, Vienna Competence Center, Vienna, Austria.
3
Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria.
4
Laboratory for Immunological and Molecular Cancer Research, Paracelsus Medical University, Salzburg, Austria.
5
Department of Biological, Geological, and Environmental Sciences, University of Bologna, Bologna, Italy.
6
Allergy Clinic Reumannplatz, Vienna, Austria.

Abstract

BACKGROUND:

Ragweed 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.

METHODS:

After 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.

RESULTS:

Amb 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.

CONCLUSION:

The 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.

KEYWORDS:

Amb a 1 allergen; allergenicity; cross-reactivity; immunogenicity; ragweed pollen allergy

PMID:
28464293
PMCID:
PMC5700413
DOI:
10.1111/all.13196
[Indexed for MEDLINE]
Free PMC Article

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