Kinetics of Antibody Responses and Effector Cell Sensitivity After High Dose Birch Extract Nasal Challenge

BACKGROUND: In allergic rhinitis (AR), effector cell activation via allergen-specific (s) IgE cross-linking is well established, yet the in vivo kinetics of allergen-specific antibody responses and their modulation of effector cell reactivity after nasal allergen exposure warrant further investigation. We therefore set out to characterize the sequence and timing of systemic and local antibody responses and basophil/mast cell sensitivity after nasal allergen challenge, and their influence on subsequent seasonal responses.

METHODS: In this randomized, double-blind, placebo-controlled trial, birch pollen-allergic adults received three daily nasal challenges with birch pollen extract (n = 20) or placebo (n = 10) in autumn. sIgE, sIgG, sIgG1, sIgG4 and sIgA levels, basophil activation (BAT), and titrated skin prick test (tSPT) responses were measured biweekly in nasal mucosal lining fluid (nMLF), blood and skin for 3 months, and before, during, and after seasonal exposure.

RESULTS: Allergen but not placebo challenge induced sequential sIgE rises, first in serum, then nMLF, mirrored by sIgG responses. Basophil sensitivity peaked with serum sIgE at 4 weeks, followed by maximal mast cell sensitivity in tSPT at 8 weeks. Allergen-specific antibodies remained elevated through the pre-seasonal and seasonal periods. Allergen-challenged subjects showed reduced sIgE rise and lower effector cell sensitivity during the following pollen season.

CONCLUSION: Out-of-season high-dose nasal allergen exposure enhances sIgE levels and effector cell sensitivity as well as sIgG and nasal sIgA responses. The latter appear to later attenuate seasonal amplification of allergic responses.

TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03644680.