Nasal Allergen Neutralising IgG4 Antibodies Block IgE-mediated Responses: Novel biomarker of Subcutaneous Grass Pollen Immunotherapy

Publication date: Available online 14 November 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): Mohamed H. Shamji, Jasper Kappen, Hisham Abubakar-Waziri, Jinjin Zhang, Esther Steveling, Shelley Watchman, Lubna Kouser, Aarif Eifan, Amy Switzer, Gilda Varrichi, Gianni Marone, Natália C. Couto-Francisco, Moises Calderon, Stephen R. Durham

Abstract

Background

Grass pollen subcutaneous immunotherapy (SCIT) is associated with induction of serum IgG₄-associated inhibitory antibodies that prevent IgE-facilitated allergen binding to B cells.

Objective

To determine whether SCIT induces nasal allergen-specific IgG₄ antibodies with inhibitory activity that correlate closely with clinical response.

Methods

In a cross-sectional, controlled study, nasal fluid and sera were collected during the grass pollen season from 10 SCIT-treated patients, 13 untreated allergics (SAR) and 12 non-atopic controls (NA). Nasal and serum IgE and IgG₄ to Phleum pratense (Phl p) components were measured by ISAC microarray. Inhibitory activity was measured by IgE-FAB assay. IL-10⁺Breg cells were quantified in peripheral blood by flow cytometry.

Results

Nasal and serum Phl p1 and Phl p5-specific IgE levels were elevated in SAR compared to NA (all, P < .001) and SCIT group. Nasal IgG₄ levels were increased in SCIT compared to SAR group (P < .001) during the pollen season compared to out of season. IgG-associated inhibitory activity in nasal fluid and serum was significantly increased in SCIT compared to SAR group (both, P < .001). The magnitude of the inhibitory activity was 96% in the nasal fluid compared to 66% in serum and was reversed following depletion of IgG in nasal fluid (P = .03) and serum (P = .002). Both nasal fluid (r = -0.67, P = .0011) and serum (r = -0.59, P = .0097) blocking activity correlated global symptom improvement. IL-10⁺Breg cells were increased in season compared to out of season in SCIT group (P < .01).

Conclusion

For the first time, we show that nasal IgG₄-associated inhibitory activity correlate closely with the clinical response to allergen immunotherapy in allergic rhinitis with/without asthma.

Graphical abstract

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