IgA⁺memory B-cells are significantly increased in patients with asthma and small airway dysfunction

Abstract

BackgroundComprehensive 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.MethodsIn 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.ResultsPatients 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.ConclusionsWith 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.

Screening and identification of tissue-infiltrating immune cells and genes for patients with emphysema phenotype of COPD

“…Memory B cells are generated upon the first encounter with a pathogen and can enhance responses to secondary antigen stimulation. A recent study found that the number of IgA+ memory B cells was significantly increased in patients with small airway dysfunction (25). Another study also found an increase in IgA+ B cells in peripheral lung tissue of patients with severe COPD, possibly due to intraluminal sIgA deficiency.…”

Long noncoding RNA antisense noncoding RNA in the INK4 locus inhibition alleviates airway remodeling in asthma through the regulation of the microRNA‐7‐5p/early growth response factor 3 axis

“… 43 IgA positive memory B cells are significantly increased in patients with asthma and small airway dysfunction, which indicates the direction for future selection of asthma prevention and treatment strategies guided by B cells. 44 …”

“…The level of C4Ma3 is elevated in the phenotype of severe and aggravating allergic asthma, and C4Ma3 can be used as a new biomarker to predict the response to anti IgE treatment 43 . IgA positive memory B cells are significantly increased in patients with asthma and small airway dysfunction, which indicates the direction for future selection of asthma prevention and treatment strategies guided by B cells 44 …”

“…43 IgA positive memory B cells are significantly increased in patients with asthma and small airway dysfunction, which indicates the direction for future selection of asthma prevention and treatment strategies guided by B cells. 44 Currently, airway remodeling in asthma remains an intractable challenge. According to previous reports, lncRNAs play a significant role in regulating the proliferation and migration of ASMCs.…”

IgA-producing B cells in lung homeostasis and disease

“…In asthma, an association was recently described between disease severity and increased blood IgA + B cells in a cohort of 154 patients and 28 healthy individuals (147). Using flow cytometry, this study showed that more severe asthma was associated with a decrease of circulating naïve and transitional B cells and an increase of IgA + B cells compared to controls as well as compared to patients with mild asthma (147). It was also described that BAFF levels were increased in lung tissue and BAL (but not in serum) in human asthma (148,149).…”