IgA+memory B-cells are significantly increased in patients with asthma and small airway dysfunction
Authors: Habener Anika , Grychtol Ruth , Gaedcke Svenja , DeLuca David , Dittrich Anna-Maria , Happle Christine , Abdo Mustafa , Watz Henrik , Pedersen Frauke , König Inke Regina , Thiele Dominik , Kopp Matthias Volkmar , von Mutius Erika , Bahmer Thomas , Rabe Klaus Friedrich , Meyer-Bahlburg Almut , Hansen Gesine ,   the ALLIANCE Study Group as part of the German Center for Lung Research (DZL), Fuchs Oliver , Roesler Barbara , Welchering Nils , Kohistani-Greif Naschla , Kurz Johanna , Landgraf-Rauf Katja , Laubhahn Kristina , Maison Nicole , Liebl Claudia , Schaub Bianca , Ege Markus , Illi Sabina , Hose Alexander , Zeitlmann Esther , Berbig Mira , Marzi Carola , Schauberger Christina , Zissler Ulrich , Schmidt-Weber Carsten , Ricklefs Isabell , Diekmann Gesa , Liboschik Lena , Voigt Gesche , Sultansei Laila , Weckmann Markus , Nissen Gyde , Kirsten Anne-Marie , Waschki Benjamin , Herzmann Christian , Biller Heike , Gaede Karoline I. , Bovermann Xenia , Steinmetz Alena , Husstedt Berrit Liselotte , Nitsche Catharina , Veith Vera , Szewczyk Marlen , Brinkmann Folke , Malik Aydin , Schwerk Nicolaus , Dopfer Christian , Price Mareike , Jirmo Adan Chari , Liu Bin , Calveron Mifflin-Rae , Weber Stefanie , Foth Svenja , Skevaki Chrysanthi , Renz Harald , Meyer Meike , Schildberg Tom , Rietschel Ernst , van Koningsbruggen-Rietschel Silke , Alcazar Miguel 
Published: May 2022

Background

Comprehensive studies investigated the role of T-cells in asthma which led to personalised treatment options targeting severe eosinophilic asthma. However, little is known about the contribution of B-cells to this chronic inflammatory disease. In this study we investigated the contribution of various B-cell populations to specific clinical features in asthma.

Methods

In the All Age Asthma Cohort (ALLIANCE), a subgroup of 154 adult asthma patients and 28 healthy controls were included for B-cell characterisation by flow cytometry. Questionnaires, lung function measurements, blood differential counts and allergy testing of participants were analysed together with comprehensive data on B-cells using association studies and multivariate linear models.

Results

Patients with severe asthma showed decreased immature B-cell populations while memory B-cells were significantly increased compared with both mild–moderate asthma patients and healthy controls. Furthermore, increased frequencies of IgA+memory B-cells were associated with impaired lung function and specifically with parameters indicative for augmented resistance in the peripheral airways. Accordingly, asthma patients with small airway dysfunction (SAD) defined by impulse oscillometry showed increased frequencies of IgA+memory B-cells, particularly in patients with mild–moderate asthma. Additionally, IgA+memory B-cells significantly correlated with clinical features of SAD such as exacerbations.

Conclusions

With this study we demonstrate for the first time a significant association of increased IgA+memory B-cells with asthma and SAD, pointing towards future options for B-cell-directed strategies in preventing and treating asthma.