Role of Der p 1-specific B cells in immune tolerance during 2-year house dust mite-specific immunotherapy

Publication date: Available online 5 December 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): Tadech Boonpiyathad, Willem van de Veen, Oliver Wirz, Milena Sokolowska, Beate Rückert, Ge Tan, Atik Sangasapaviliya, Panitan Pradubpongsa, Rattanaporn Fuengthong, Pattarawat Thantiworasit, Sunee Sirivichayakul, Kiat Ruxrungtham, Cezmi A. Akdis, Mübeccel Akdis

Abstract

Background

Long-term follow-up of allergen-specific B cells in terms of immunoglobulin isotype expression, plasmablasts differentiation and regulatory B cell (Breg) development during allergen-specific immunotherapy (AIT) has not been reported.

Objective

Allergen-specific B cell responses during 2-years house dust mite (HDM) AIT were compared between responder and non-responder patients.

Methods

B cells specific for the Der p 1 were detected using fluorochrome-labeled allergen method. Frequency of IgA-, IgG1- and IgG4-switched Der p 1-specific B cells, plasmablasts and IL-10 and IL-1RA-producing Breg cells were investigated and correlated to clinical response to AIT.

Results

Sixteen of 25 patients completed the 2-year study. Eleven responder patients showed a successful response to AIT as measured by decreased symptom medication score from 13.23 ± 0.28 to 2.45 ± 0.24, P = 0.001 and decreased skin prick test reactivity to HDM from 7.0 ± 1.3 mm to 2.7 ± 0.5 mm, P = 0.001. IgG4⁺ and IgA⁺ Der p 1-specific B cells showed a significant increase after AIT, with a significantly higher frequency in responders compared to non-responder patients in IgG4⁺ but not in IgA⁺ fraction. The frequency of plasmablasts, IL-10 and/or IL-1RA-producing Breg cells was higher among responders compared to non-responders after 2 years. Increased frequency of Der p 1-specific IgG4⁺ B cells, plasmablasts, IL-10⁺ and dual positive IL-10⁺IL-1RA⁺ Breg cells significantly correlated with improved clinical symptoms over the course of AIT.

Conclusion

Allergen-specific B cells in therapy responder patients in AIT are characterized with increased IgA- and IgG4-expressing Der p 1-specific B cells, plasmablasts and IL-10⁺ and/or IL-1RA⁺ Breg cells.

Graphical abstract

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