Effects of birch pollen SIT on apple allergy: a matter of dosage?

The efficacy and long-term effect of injection allergenspecific immunotherapy (SIT) in the treatment of respiratory allergies have been established by a number of studies and are generally accepted (1, 2). Recent findings suggest that the clinical effect of SIT relies essentially on two main immunological mechanisms, namely immunedeviation (a shift towards a Th1 immune response) possibly mediated by IL-12, the strongest inducer of Th1 responses known (3), and immune tolerance induced by IL-10, an immunosuppressive cytokine (4). SIT is presently not accepted as a treatment for food allergies, and allergen avoidance remains the only way to prevent potentially life-threatening reactions in patients sensitized to foods. Yet, curing food allergies by SIT probably remains the secret dream of many clinical allergologists. Some experimental attempts to desensitize peanut-allergic patients proved effective although, probably because of the lack of proper allergen standardization, both the build-up phase and the maintenance protocol were associated with an unacceptably high rate of adverse systemic reactions (5, 6). The pollen-food allergy syndrome shows some advantageous features that make it a unique opportunity to evaluate the effect of SIT on food allergies. First, the risk of adverse reactions is minimal as SIT is carried out using the same well-standardized and safe pollen extracts that are widely used in thousands of allergic patients. In the pollen-food allergy syndrome, it is pollen that causes primary sensitization (7), and food allergy results from the immunological cross-reactivity between allergens in pollen and plant-derived foods (8–11); several lines of evidence suggest that virtually all allergenic epitopes of foods are present in pollen (8–10, 12). Secondly, because of the extreme lability of the relevant proteins, allergic symptoms induced by foods are generally mild and limited to oral allergy syndrome (OAS), a fact that allows food challenges to be performed without the fear of exposing patients to severe or even life-threatening allergic reactions (13). In the present issue of Allergy, Bucher et al. analyze the effect of 1 year of injection SIT with birch pollen extract in a group of birch pollen-allergic subjects with OAS induced by apple or hazelnut. Notably, most patients studied were not monosensitized to birch pollen, which means that at least part of them were probably sensitized both to Bet v 1 and to other cross-reacting allergens, particularly profilin. After 1 year of immunotherapy, the patients showed an increased rate of skin reactivity to fresh apple, but 87% of them (vs only 8% of controls) could tolerate a significantly higher amount of offending food. However, as the average amount of apple/hazelnut tolerated by SIT-treated patients remained relatively small (32 g) Bucher et al. s conclusion is that SIT has only limited effects on OAS. Only six other studies dealt with the effects of injection SIT (with birch pollen in four studies, and different pollens in two) on food allergy in patients with pollen-food allergy syndrome before. Moller (14) observed a reduction of food-induced reactions in 43% of his birch pollen-allergic pediatric patients vs 14% of controls but, because of the lack of a statistically significant difference between the study groups, concluded that SIT is not effective in reducing birch pollenrelated food allergies. Herrmann et al. (15) noted an improvement of food allergy in 45% of patients submitted to injection SIT with birch pollen extract. More recently 41 of 49 (84%) adults monosensitized to birch pollen reported a significant reduction or the total disappearance of their apple-induced OAS after 1 year of injection SIT (16); the clinical effect was associated with a marked reduction or with the total disappearance of skin reactivity to fresh apple and was rather longR. Asero Ambulatorio di Allergologia, Clinica San Carlo, Paderno Dugnano, Italy