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

Date Published: December 12, 2017

Publisher: John Wiley and Sons Inc.

Author(s): J. Eckl‐Dorna, R. Fröschl, C. Lupinek, R. Kiss, P. Gattinger, K. Marth, R. Campana, I. Mittermann, K. Blatt, P. Valent, R. Selb, A. Mayer, K. Gangl, I. Steiner, J. Gamper, T. Perkmann, P. Zieglmayer, P. Gevaert, R. Valenta, V. Niederberger.

http://doi.org/10.1111/all.13343

Abstract

Administration of the therapeutic anti‐IgE antibody omalizumab to patients induces strong increases in IgE antibody levels.

To investigate the effect of intranasal administration of major birch pollen allergen Bet v 1, omalizumab or placebo on the levels of total and allergen‐specific IgE in patients with birch pollen allergy.

Based on the fact that intranasal allergen application induces rises of systemic allergen‐specific IgE, we performed a double‐blind placebo‐controlled pilot trial in which birch pollen allergic subjects were challenged intranasally with omalizumab, placebo or birch pollen allergen Bet v 1. Total and allergen‐specific IgE, IgG and basophil sensitivity were measured before and 8 weeks after challenge. For control purposes, total, allergen‐specific IgE levels and omalizumab‐IgE complexes as well as specific IgG levels were studied in subjects treated subcutaneously with either omalizumab or placebo. Effects of omalizumab on IgE production by IL‐4/anti‐CD40‐treated PBMCs from allergic patients were studied in vitro.

Intranasal challenge with Bet v 1 induced increases in Bet v 1‐specific IgE levels by a median of 59.2%, and this change differed significantly from the other treatment groups (P = .016). No relevant change in allergen‐specific and total IgE levels was observed in subjects challenged with omalizumab. Addition of omalizumab did not enhance IL‐4/anti‐CD40‐induced IgE production in vitro. Significant rises in total IgE (mean IgE before: 131.83 kU/L to mean IgE after: 505.23 kU/L) and the presence of IgE‐omalizumab complexes were observed after subcutaneous administration of omalizumab.

Intranasal administration of allergen induced rises of allergen‐specific IgE levels, whereas intranasal administration of omalizumab did not enhance systemic total or allergen‐specific IgE levels.

Partial Text

Immunoglobulin E (IgE) is the key antibody class responsible for allergic symptoms in sensitized patients.1 Cross‐linking of IgE bound to the surface of mast cells and basophils via its high‐affinity receptor (FcεRI) results in degranulation of the cells and the release of inflammatory mediators, cytokines and proteases.2, 3, 4

In the present study, we investigated the effect of intranasal administration of Bet v 1, omalizumab and placebo on the levels of total and allergen‐specific IgE in patients with birch pollen allergy. The pilot clinical trial performed by intranasal administration of Bet v 1 and omalizumab was based on the observation that intranasal administration of allergen to allergic patients induced a robust increase in allergen‐specific IgE antibodies, eventually by targeting IgE‐producing cells.20, 21, 22, 23 In fact, histological analyses of nasal mucosal biopsies have revealed the presence of IgE+ B cells and plasma cells in the nasal mucosa.18 Furthermore, Sε switch circles have been found in nasal biopsies after ex vivo allergen challenge suggesting local synthesis of IgE in the nasal mucosa.19 We therefore hypothesized that IgE‐producing B cells in the nasal mucosa are the source of the allergen‐induced systemic IgE rises and can be reached and stimulated via the intranasal route. Indeed, we were able to demonstrate that nasal administration of the major birch pollen allergen Bet v 1 led to a significant increase in Bet v 1‐specific IgE levels 5 weeks after the challenge. Interestingly, these increases in Bet v 1‐specific IgE levels observed after 5 weeks did not lead to increased basophil sensitivity when basophils of allergic patients were exposed to the Bet v 1 allergen. In contrast, when we passively sensitized basophils with serum taken at the same time, an increased Bet v 1‐specific basophil sensitivity was observed.

Rudolf Valenta has received research grants from Biomay AG, Vienna, Austria; Thermofisher, Uppsala, Sweden; Fresenius Medical Care, Bad Homburg, Germany; and Viravaxx, Vienna, Austria, and serves as a consultant for these companies. Dr. Marth reports personal fees from Novartis, personal fees from Thermofisher, personal fees from Teva, personal fees from Medmedia, non‐financial support from Boehringer Ingelheim, personal fees from Chiesi, outside the submitted work. Dr. Valenta reports grants from FWF, during the conduct of the study; grants and other from Biomay, grants and other from Viravaxx, outside the submitted work. Dr. Philippe reports grants and personal fees from Novartis, Roche, Genentech, during the conduct of the study. Dr. Lupinek reports personal fees from Thermo Fisher Scientific, outside the submitted work. Dr. Selb reports grants from Austrian Research Fund (FWF), during the conduct of the study. The other authors declare that they have no conflicts of interest.

RV and VN designed and planned this study, participated in the interpretation of the findings, wrote, read and critically revised the manuscript. JED contributed to design and planning of the study, performed the data analyses, participated in the interpretation of the findings and wrote the initial manuscript and read and revised the final version. RF, RK, CL and TP performed measurements for specific and total IgE levels (CAP and CHIP measurements), read and revised the manuscript. PG and IM performed RBL assays, and KB and PV conducted basophil activation assays, read and revised the manuscript. RS, KM, RC, PZ, AM, KG assisted in planning and performing the intranasal challenge study, read and revised the manuscript. PhG kindly provided sera for analysis of subjects having received subcutaneous administration of omalizumab, read and revised the manuscript. IS and JG performed statistical analyses, read and revised the manuscript.

 

Source:

http://doi.org/10.1111/all.13343

 

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