Omalizumab's Impact on Total and Allergen-Specific IgE Levels: A Polyclonal Story

Abstract

the rapid decrease in free serum IgE levels was noticed [3, 4] . However, the impact of omalizumab on changes in allergen-specific IgE levels has so far not been investigated. In a recent issue of the International Archives of Allergy and Immunology , Mizuma et al. [5] were the first to report changes not only in the levels of total IgE but also of allergen-specific IgE. The authors retrospectively determined changes in allergen-specific IgE levels for 11 different aeroallergens in 47 asthma patients treated with omalizumab and 30 treated with placebo. In previously sensitized patients, they observed a significant rise in allergen-specific IgE levels upon treatment with omalizumab. The changes in allergen-specific IgE levels positively correlated with baseline IgE levels. Remarkably, using the well-established cut-off value of 0.35 kU/l for sensitization, they observed a negative-topositive seroconversion rate of up to 30% for some allergens, such as Japanese cedar, upon omalizumab treatment. The fact that seroconversion was not observed for all allergens may be due to the small sample size of 47 patients, only some of whom were not previously sensitized to the relevant allergens. Information about patients undergoing seroconversion being symptomatic for the respective allergens before showing the relevant IgE levels were only available for one allergen, Japanese cedar. All 4 patients were already suffering from pollinosis before In 1966, Kimishige and Teruko Ishizaka [1] were the first to precipitate and characterize ‘reaginic antibodies’ from sera of atopic patients. As the newly identified antibody was different from the four immunoglobulin isotypes known at that time, it was designated IgE. Interestingly, preabsorption of serum from ragweed allergic patients with ‘anti-γE’ serum raised in rabbits abolished the passive skin sensitizing activity of the serum as measured by the Prausnitz-Kuestner reaction. Thus IgE and its link to allergy were discovered. Already in the aforementioned study, IgE-specific antibodies raised in animals were used to block the effects of IgE in experimental settings. However, it took more than 2 decades until Presta et al. [2] at Genentech developed the first humanized IgG1 antibody directed against IgE and intended for therapeutic usage in 1993. This antibody, rhuMAb-E25, also called omalizumab, was designed to bind to the Ce3 region of free IgE and thus block the binding of IgE to the FceRI present on mast cells and basophils. It decreases serum levels of free IgE by more than 95%. From a clinical point of view, therapy with omalizumab reduces asthma exacerbations and the use of rescue medication in adults and children suffering from allergic asthma. Interestingly, already in the first clinical studies with omalizumab, an increase in total IgE levels accompanying Published online: April 2, 2016