Sublingual exposure to apple may build tolerance in birch pollen-allergic patients

Published Online: August 27, 2012

In addition to their respiratory symptoms more than 70% of birch pollen-allergic patients develop allergic reactions to particular foods, most often apples. This birch pollen-related food allergy results from cross-reactivity of IgE antibodies and T cells specific for the major birch pollen allergen Bet v 1 with the structurally related apple protein Mal d 1. It is known that respiratory exposure to birch pollen during the pollen season boosts the allergic response to Bet v 1. However, possible in vivo consequences of ingestion of cross-reactive food allergens on the immune response to the major birch pollen allergen are largely unknown.

In an article published in The Journal of Allergy & Clinical Immunology (JACI) the team of B. Bohle has investigated the effects of ingestion of apple on the allergen-specific immune response in birch pollen-allergic patients. To perform food exposure under defined experimental conditions birch pollen-allergic patients sublingually received 50 µg of recombinant Mal d 1 (roughly corresponding to the Mal d 1 content of one apple) on two consecutive days outside of the birch pollen season. This approach allowed oral exposure to precise amounts of pure apple allergen and the comparison with equal amounts of recombinant Bet v 1 which were sublingually administered to the same individuals one year later. Clinical reactions to either recombinant allergen as well as changes of Bet v 1- and Mal d 1-specific IgE levels and T cell responses (proliferative and cytokine responses) were assessed.

The authors found that two sublingual administrations of 50 µg of Mal d 1 were well tolerated and significantly reduced Mal d 1- and Bet v 1-specific serum IgE levels. Furthermore, oral exposure to Mal d 1 induced activation of allergen-specific Th2 cells together with induction of transient peripheral tolerance, possibly mediated by IL-10+Foxp3+ T cells with suppressive capacity. Similar effects were observed upon oral exposure to Bet v 1. Of note, oral exposure to Mal d 1 triggered a different population of allergen-specific T lymphocytes than oral exposure to Bet v 1.

The authors´ findings provide strong evidence that sublingual administration of recombinant Mal d 1 induces immunological tolerance. Thus, recombinant Mal d 1 may be suitable and relevant for sublingual treatment of birch pollen-related apple allergy.


The Journal of Allergy and Clinical Immunology (JACI) is the official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.

AAAAI - American Academy of Allergy Asthma & Immunology