Effects of birch pollen-specific immunotherapy on apple allergy in birch pollen-hypersensitive patients

Background Most patients with birch pollen allergy report oral allergy symptoms after eating fresh apples and other vegetable foods. Major birch pollen and apple allergens, Bet v 1 and Mal d 1, are highly homologous; as a consequence, pollen-specific immunotherapy (SIT) might be expected to improve apple hypersensitivity. Objective To evaluate the clinical and immunological effects of birch pollen SIT on oral allergy syndrome (OAS) induced by apples. Methods A prospective study carried out in 49 birch pollen-sensitive patients with apple-induced OAS who received injection immunotherapy for 12, 24, or 36 months. Twenty-six patients not submitted to SIT and followed up for 12-48 months were used as controls. Both SPT and open oral challenges with fresh golden delicious apple were performed, as well as specific IgE measurements, before and after SIT. Results Forty-one patients (84%) vs no control (0%) reported a significant reduction (50-95%) or a total disappearance (100%) of OAS symptoms after SIT (P<0.001). Similar responses were observed in patients treated for 12, 24, or 36 months. SIT also induced a marked reduction in skin reactivity against fresh apple in 43 patients (88%). The effect of SIT was inversely related with baseline skin reactivity: 50% and 8% patients with a weakly or strongly positive baseline apple skin prick tests (SPT), respectively, did not report changes in OAS severity after SIT (P < 0.01). In contrast, baseline birch pollen-specific or apple-specific IgE antibodies levels did not influence SIT effectiveness on GAS. SIT induced a marked decrease in birch pollen-specific IgE levels (P < 0.001), whereas apple-specific IgE showed an unexpected variability (reduction in 21%, no change in 43%, increase in 38%). No control subject reported a reduction in OAS severity or showed a decrease in skin reactivity at follow-up (P<0.001). Conclusions SIT with birch pollen extracts effectively reduces clinical apple sensitivity and skin reactivity in most cases after only 1 year of treatment; these effects are not paralleled by a similar reduction in apple-specific IgE. These findings suggest a decrease in activability of effector cells as the mechanism underlying clinical benefit.