Abstract
Background Comprehensive studies investigated the role of T cells in asthma leading 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 via 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 to both mild-moderate asthma patients and healthy controls. Furthermore, increased frequencies of immunoglobulin A positive (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 to 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.
Footnotes
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Christine Happle reports grants from Novartis and Pari, outside the submitted work.
Matthias Volkmar Kopp reports grants from Allergopharma GmbH, Vertex GmbH; honoraria for lectures from Allergopharma GmbH, Sanofi GmbH, Infectopharm GmbH, Vertex GmbH, Leti GmbH; Advisory Board membership at Allergopharma GmbH, Sanofi GmbH; outside the submitted work.
Erika von Mutius reports royalties from Elsevier GmbH, Georg Thieme Verlag, Springer-Verlag GmbH, Elsevier Ltd.; consulting fees from Chinese University of Hongkong, European Commission, HiPP GmbH & Co KG, AstraZeneca; lecture honoraria from Massachusetts Medical Society, Springer-Verlag GmbH, Elsevier Ltd., Böhringer Ingelheim International GmbH, European Respiratory Society (ERS), Universiteit Utrecht, Faculteit Diergeneeskunde, Universität Salzburg, Springer Medizin Verlag GmbH, Japanese Society of Pediatric Allergy and Clinical Immunology (JSPACI), Klinikum Rechts der Isar, University of Colorado, Paul-Martini-Stiftung, Imperial College London; travel support from Verein zur Förderung der Pneumologie am Krankenhaus Großhansdorf e.V., Pneumologie Developpement, Mondial Congress & Events GmbH & Co. KG, American Academy of Allergy, Asthma & Immunology, Imperial College London, Margaux Orange, Volkswagen Stiftung, Böhringer Ingelheim International GmbH, European Respiratory Society (ERS), Universiteit Utrecht, Faculteit Diergeneeskunde, Österreichische Gesellschaft f. Allergologie u. Immunologie, Massachusetts Medical Society, OM Pharma S. A., Hanson Wade Ltd., iKOMM GmbH, DSI Dansk Borneastma Center, American Thoracic Society, HiPP GmbH & Co KG, Universiteit Utrecht, Faculteit Bètawetenschappen; outside the submitted work. In addition, EvM has patent LU101064 (Barn dust extract for the prevention and treatment of diseases) pending, royalties paid to ProtectImmun for patent EP2361632 (Specific environmental bacteria for the protection from and/or the treatment of allergic, chronic inflammatory and/or autoimmune disorders, granted on 19 March 2014), and patents EP1411977 (Composition containing bacterial antigens used for the prophylaxis and the treatment of allergic diseases, granted on 18 April 2007), EP1637147 (Stable dust extract for allergy protection, granted on 10 December 2008), and EP 1964570 (Pharmaceutical compound to protect against allergies and inflammatory diseases, granted on 21 November 2012) licensed to ProtectImmun. In addition, EvM is a member of the EXPANSE (funded by European Commission) Scientific Advisory Board, Member of the BEAMS External Scientific Advisory Board (ESAB), Member of the Editorial Board of “The Journal of Allergy and Clinical Immunology: In Practice”, Member of the Scientific Advisory Board of the Children's Respiratory and Environmental Workgroup (CREW), Member of the International Scientific & Societal Advisory Board (ISSAB) of Utrecht Life Sciences (ULS), University of Utrecht, Member of External Review Panel of the Faculty of Veterinary Science, University of Utrecht, Member of the Selection Committee for the Gottfried Wilhelm Leibniz Programme (DFG), Member of the International Advisory Board of Asthma UK Centre for Applied Research (AUKCAR), Member of the International Advisory Board of “The Lancet Respiratory Medicine”, Member of the Scientific Advisory Board of the CHILD (Canadian Healthy Infant Longitudinal Development) study, McMaster University, Hamilton, Canada.
Thomas Bahmer reports grants from Network University Medicine (NUM): National Pandemic Cohort Network (NAPKON); consulting fees and lecture honoraria from Astra Zeneca, Novartis, GlaxoSmithKline, Roche, Chiesi; travel support from Chiesi, Astra Zeneca; outside the submitted work.
Klaus F. Rabe reports lecture honoraria from AstraZeneca, Boehringer Ingelheim, Chiesi Pharmaceuticals, Novartis, Sanofi & Regeneron, GlaxoSmithKline, Berlin Chemie, Roche; Advisory Board membership at AstraZeneca, Sanofi Regeneron; leadership roles with German Center for Lung Research (DZL), German Chest Society (DGP), American Thoracic Society (ATS); outside the submitted work.
Almut Meyer-Bahlburg reports lecture honoraria from Pfizer; travel support from CSL Behring; Advisory Board membership with Pfizer; outside the submitted work.
Gesine Hansen reports consulting fees from Sanofi GmbH; lecture honoraria from MedUpdate, Abbvie; outside the submitted work.
All other authors have nothing to disclose.
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- Received August 16, 2021.
- Accepted March 25, 2022.
- Copyright ©The authors 2022. For reproduction rights and permissions contact permissions{at}ersnet.org