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