Influence of Omalizumab on Allergen-Specific IgE in Patients with Adult Asthma

Abstract

Background: Omalizumab, an anti-immunoglobulin E (IgE) monoclonal antibody, inhibits the binding of circulating IgE to mast cells and basophils, resulting in fewer episodes of airway inflammation, asthma symptoms and exacerbations in patients with severe allergic asthma. Treatment of patients with asthma using omalizumab increases serum total IgE (tIgE) levels. However, little is known about the influence of omalizumab on allergen-specific IgE (sIgE). Methods: tIgE and sIgE in 47 adult patients with severe asthma were measured with a fluorescent enzyme immunoassay (ImmunoCAP-FEIA) before and after omalizumab treatment. Results: Treatment with omalizumab increased tIgE and sIgE levels. The increases in sIgE by class category after omalizumab treatment were positively correlated with baseline sIgE positivity before treatment. The mean changes in sIgE levels after omalizumab treatment were also correlated with baseline sIgE levels before treatment. The mean changes in tIgE levels were positively correlated with the mean changes in IgE levels against Dermatophagoides pteronyssinus, crude house dust, Japanese cedar and moth. Omalizumab markedly influenced the negative-to-positive seroconversion rate for IgE against Japanese cedar (30.8%), Candida (29.0%) and moth (28.0%). Finally, all patients with negative-to-positive seroconversion for Japanese cedar-specific IgE had cedar pollinosis before beginning omalizumab treatment. Conclusions: The changes in sIgE levels after omalizumab treatment may be dependent on the baseline sIgE levels. Our data may indicate the presence of undetectable but functional sIgE.

Seasonal Exacerbation of Asthma Is Frequently Associated with Recurrent Episodes of Acute Urticaria

“…In both conditions, IgE is frequently elevated and anti-IgE therapy is highly effective. They also improve in response to glucocorticosteroids, and antihistamines are widely used in their treatment [4,5,6]. Based on these similarities, researchers suspect that asthma and urticaria are linked and that they frequently occur in the same patient.…”

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

“…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.…”

Intranasal administration of allergen increases specific IgE whereas intranasal omalizumab does not increase serum IgE levels—A pilot study

“…Only in 3 patients, IgE sensitization to cat and mite allergens exceeding cut‐off IgE levels was noted. This observation is in line with a recent study conducted by Mizuma et al., where the authors described patients while exhibiting Japanese cedar‐specific IgE levels above 0.35 kU/L only after omalizumab therapy had already suffered from cedar pollinosis before therapy 13, 14. Using an assay able to distinguish IgE‐omalizumab complexes from IgE and omalizumab alone, we could demonstrate the formation of IgE‐omalizumab complexes after subcutaneous omalizumab administration, which correlated to some extent with the increase in total IgE.…”

“…It is therefore possible that cross‐linking of the BCR on IgE + memory cells may contribute to the strong increases in IgE levels which are observed in patients treated with omalizumab in addition to a prolongation of the half‐life of IgE within the omalizumab‐IgE immune complexes 5, 13, 14. In this context, it has recently been hypothesized that the binding of omalizumab to IgE may prevent degradation of IgE via binding of the resulting IgE‐IgG complex to the neonatal Fc receptor (FcRn) and thus protecting it from endolysosomal degradation or that the IgE‐omalizumab complexes do not undergo pinocytosis 15.…”