Allergic conversion of protective mucosal immunity against nasal bacteria in chronic rhinosinusitis with nasal polyposis

Publication date: Available online 25 July 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): Kazuya Takeda, Shuhei Sakakibara, Kazuo Yamashita, Daisuke Motooka, Shota Nakamura, Marwa Ali El Hussien, Jun Katayama, Yohei Maeda, Masanobu Nakata, Shigeyuki Hamada, Daron M. Standley, Masaki Hayama, Takashi Shikina, Hidenori Inohara, Hitoshi Kikutani

Abstract

Background

Chronic rhinosinusitis with nasal polyposis (CRSwNP) is characterized by eosinophilic inflammation and polyposis at the nose and paranasal sinus and a high concentration of IgE in nasal polyps (NPs). The causative antigen and pathogenesis of CRSwNP remain unknown.

Objective

We aimed to identify reactive allergens of IgE antibodies produced locally in NPs of CRSwNP patients. We also attempted to unravel the differentiation pathway of IgE-producing B cells in the NPs.

Methods

IgE reactivity of CRSwNP patients was investigated by characterizing single cell-derived monoclonal antibodies. T cell response against identified allergens was investigated in vitro. NP-infiltrating lymphocytes were characterized by flow cytometry. Immunoglobulins expressed in NPs were analyzed by high-throughput immunoglobulin (HTS Ig) sequencing.

Results

About 20% of isolated IgE antibodies derived from NP-residing plasmablasts (PBs) specifically recognized surface determinants of nasal bacteria such as Staphylococcus aureus, Streptococcus pyogenes, and Haemophilus influenzae. A Th2 response against S. pyogenes was observed in CRSwNP patients. Flow cytometric analysis revealed sizable germinal center B-like and PB subsets expressing IgE on the cell surface in NPs. HTS Ig analysis highlighted the clonal connectivity of IgE with IgG and IgA₁. The Iε−Cα₁ circle transcript was detected in NPs.

Conclusions

In CRSwNP patients, nasal bacteria-reactive B cells differentiate into IgE-producing B cells through IgG/A₁-IgE class switching, suggesting that allergic conversion of the mucosal response against nasal bacteria underlies disease pathogenesis.

Graphical abstract

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