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. 2018 May 18:16:13.
doi: 10.1186/s12948-018-0091-x. eCollection 2018.

Regulation of IgE activity in inhalational tolerance via formation of IgG anti-IgE/IgE immune complexes

Sonali J Bracken  1 , Alexander J Adami  1 , Ektor Rafti  2 , Craig M Schramm  2 , Adam P Matson  1   2
Affiliations

Regulation of IgE activity in inhalational tolerance via formation of IgG anti-IgE/IgE immune complexes

Sonali J Bracken et al. Clin Mol Allergy. .

Abstract

Background: Allergic asthma is an inflammatory disorder of the airways that results from inappropriate production of IgE against harmless, environmental antigens. Sequestration of free IgE using humanized IgG anti-IgE is an effective therapy for asthma and other atopic disorders. However, the status of free IgE in subjects who have naturally developed immune tolerance to inhaled antigens has not been well studied.

Methods: C57BL/6 mice were sensitized and challenged with ovalbumin (OVA) for 7 days to induce allergic airway disease (AAD) or 6 weeks to induce a state of local inhalational tolerance (LIT). Serum from AAD or LIT mice, diluted to achieve equivalent levels of total OVA-specific IgE, was used to sensitize rat basophil leukemia cells for allergen-mediated degranulation. Levels of degranulation were measured in relation to serum concentrations of free IgE and IgG anti-IgE/IgE immune complexes.

Results: Serum from AAD animals induced a greater degree of basophil degranulation than serum from LIT animals. These results correlated with higher levels of free IgE in AAD animals, whereas LIT mice demonstrated a significant increase in IgG anti-IgE/IgE immune complexes relative to their diseased counterparts.

Conclusions: Sequestration of free IgE by naturally occurring IgG anti-IgE may aid in the development of immune tolerance against inhaled allergens. The decrease in bioavailability of free IgE may, in turn, contribute to the overall reduction of asthma symptoms via a mechanism that mimics the therapeutic effects of humanized IgG anti-IgE.

Keywords: Anti-IgE; Asthma; Autoantibodies; Hexosaminidase; IgE; Omalizumab; Ovalbumin; Tolerance.

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Figures

Fig. 1
Fig. 1
LIT serum demonstrates a reduced capacity to elicit RBL mediator release compared to AAD serum. RBL assays were performed as described above. For AAD and LIT samples, twofold serial dilutions starting at 500 ng/ml OVA-IgE were performed. For naïve animals, samples were diluted using twofold serial dilutions from 1:1 to 1:8 concentrations. β-hexosaminidase release was measured as a percentage of total release in control samples. n = 6–8 per group. ap < 0.05 vs naïve, bp < 0.05 vs LIT
Fig. 2
Fig. 2
LIT serum contains higher levels of IgG anti-IgE/IgE immune complexes and lower free IgE levels relative to AAD serum. a Levels of IgG1 anti-IgE/IgE immune complexes were determined as described above. For naïve samples, undiluted serum was used. b Levels of free IgE were determined in samples with equal concentrations of total IgE as described above. For naïve samples, undiluted serum was used. n = 6–8 per group. *p < 0.05 vs naïve, ***p < 0.001 vs naïve, ††p < 0.01 vs AAD, †††p < 0.001 vs AAD. ND none detected
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