Broad Immunglobulin G Repertoire in Chronic Rhinosinusitis with Nasal Polyps regulates pro-inflammatory IgE responses

Publication date: Available online 11 February 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Mohamed H. Shamji, Irene Thomsen, Janice Layhadi, Jasper Kappen, Gabriële Holtappels, Umit Sahiner, Amy Switzer, Stephen R. Durham, Oliver Pabst, Claus Bachert

Abstract

Background

Chronic rhinosinusitis with nasal polyps (CRSwNP) is often characterized by local production of polyclonal IgE-idiotypes. Whilst tissue IgE concentrations can be in the range of several thousand kU/L, the regulatory mechanisms by which IgE-mediated inflammation is controlled in the nasal polyps is not well understood.

Objective

We sought to determine whether locally induced IgG antibodies in the nasal polyps can inhibit IgE-mediated pro-allergic response.

Methods

Nasal polyp homogenates were collected from grass pollen allergics with CRSwNP and non-allergic controls. IgE levels were measured by ISAC. IgE-containing nasal polyp homogenates, with/without IgG depletion, were evaluated for their capacity to promote IgE-facilitated allergen presentation, basophil activation and histamine release. Local IgE and IgG repertoires were evaluated by Immunoglobulin 454 sequencing.

Results

We show that IgG plays a key role in controlling IgE-mediated inflammatory responses in nasal polyps. Depletion of IgG from nasal homogenates resulted in an increase in CD23-mediated IgE-facilitated allergen binding to B cells (IgE-FAB), but also enhanced FcεRI-mediated allergen driven basophil activation and histamine release. A similar response was observed in relation to specific IgE antibodies to Staphylococcus aureus (SE-IgE). The capacity of IgG in nasal polyps to limit IgE-mediated inflammation is based on the fact that IgG repertoires widely share the antigen targets with the IgE repertoires, in both allergic and non-allergic subjects.

Conclusion

Polyclonal IgE idiotypes in CRSwNP are functional, promote IgE-mediated pro-allergic inflammation and are partially antagonized by corresponding IgG-idiotypes. This is most likely due to the fact that IgE and IgG clonotypes are widely shared in nasal polyps.

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