Changes in Binding Patterns of Cashew-Specific IgE and IgG4 Over the Course of Oral Immunotherapy with Omalizumab

RATIONALE: The mechanisms by which oral immunotherapy (OIT) induces desensitization are under study. Increases in the ratio of allergen-specific IgG4 to IgE have been consistently observed in OIT trials. Because recognition of major allergen proteins by IgE is associated with clinical allergy whereas IgG4 has a protective effect, changes in the diversity, quantity, and interactions of these antibodies may contribute to desensitization.

METHODS: Immunoblotting for cashew-specific IgE and IgG4 was performed for 12 cashew-allergic participants and 3 non cashew-allergic controls undergoing multi-allergen OIT with omalizumab adjuvant therapy. Binding patterns at the beginning of therapy (Week 0) were compared to binding patterns at the end (Week 36). No omalizumab was present in the blood at these two time points.

RESULTS: The number of proteins bound by IgE decreased in 8/12 participants from a mean of 4.0 proteins at Week 0 to 1.6 proteins at Week 36. The most frequently and persistently bound protein was the large subunit of Ana o 2 (9 participants at Week 0 versus 6 at Week 36). Number of proteins bound by IgG4 increased in 12/12 participants from a mean of 1.9 to 4.6 proteins. Again, the large subunit of Ana o 2 was most frequently bound (7 participants at Week 0 versus 10 at Week 36). The largest induction of IgG4 binding was observed for intact Ana o 3 (1 participant at Week 0 versus 7 at Week 36).

CONCLUSIONS: Our preliminary data suggests decreases in cashew-specific IgE and increases in cashew-specific IgG4 during cashew immunotherapy.