Differential switching to IgG and IgA in active smoking COPD patients and healthy controls

Brandsma, Corry‐Anke; Kerstjens, Huib A. M.; Geffen, Wouter H. van; Geerlings, Marie; Postma, Dirkje S.; Hylkema, Machteld N.; Timens, Wim

doi:10.1183/09031936.00011211

Cited by 39 publications

(28 citation statements)

References 46 publications

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“…CSR is an intricate process involving signalling through the B cell receptor, CD40, Toll-like receptors and cytokine responses[32]. Smoking has previously been shown to affect B cell IgG switching in COPD[33], but we observed no significant difference in the levels of BAL IgG1 or serum IgM between COPD smokers (n = 11) and COPD ex-smokers (n = 13). IFNγ has been shown to suppress IgG1 production, whilst IL-6 can enhance production of all IgG isotypes[34].…”

Section: Discussioncontrasting

confidence: 61%

Relationships between Mucosal Antibodies, Non-Typeable Haemophilus influenzae (NTHi) Infection and Airway Inflammation in COPD

et al. 2016

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Non-typeable Haemophilus influenzae (NTHi) is a key pathogen in COPD, being associated with airway inflammation and risk of exacerbation. Why some patients are susceptible to colonisation is not understood. We hypothesised that this susceptibility may be due to a deficiency in mucosal humoral immunity. The aim of our study (NCT01701869) was to quantify the amount and specificity of antibodies against NTHi in the lungs and the associated risk of infection and inflammation in health and COPD. Phlebotomy, sputum induction and bronchoscopy were performed on 24 mild-to-moderate COPD patients and 8 age and smoking-matched controls. BAL (Bronchoalveolar lavage) total IgG1, IgG2, IgG3, IgM and IgA concentrations were significantly increased in COPD patients compared to controls. NTHi was detected in the lungs of 7 of the COPD patients (NTHi+ve—29%) and these patients had a higher median number of previous exacerbations than NTHi-ve patients as well as evidence of increased systemic inflammation. When comparing NTHi+ve versus NTHi-ve patients we observed a decrease in the amount of both total IgG1 (p = 0.0068) and NTHi-specific IgG1 (p = 0.0433) in the BAL of NTHi+ve patients, but no differences in total IgA or IgM. We observed no evidence of decreased IgG1 in the serum of NTHi+ve patients, suggesting this phenomenon is restricted to the airway. Furthermore, the NTHi+ve patients had significantly greater levels of IL-1β (p = 0.0003), in BAL than NTHi-ve COPD patients.This study indicates that the presence of NTHi is associated with reduced levels and function of IgG1 in the airway of NTHi-colonised COPD patients. This decrease in total and NTHI-specific IgG1 was associated with greater systemic and airway inflammation and a history of more frequent exacerbations and may explain the susceptibility of some COPD patients to the impacts of NTHi.

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Section: Discussioncontrasting

confidence: 61%

Relationships between Mucosal Antibodies, Non-Typeable Haemophilus influenzae (NTHi) Infection and Airway Inflammation in COPD

et al. 2016

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“…However, it remains to be determined whether IL-6 is also involved in the differentiation/maturation of B-cells in the COPD lung, and whether the regulation of B-cells from COPD patients could differ from that of the normal blood B-cells used here. Thus, it was found that blood B-cells from actively smoking COPD patients could differ from healthy controls in terms of B-cell responses and immunoglobulin switching [42]. It is therefore possible that intrinsic changes could also directly affect B-cells from smokers and/or COPD patients, in addition to their abnormal conditioning by the airway epithelium, which was the focus of the present study.…”

Section: Both Maturation Of B-cells Into Cd38mentioning

confidence: 81%

Increased IgA production by B-cells in COPDvialung epithelial interleukin-6 and TACI pathways

et al. 2014

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Despite their relevance to mucosal defense, production of IgA and the function of lung B-cells remain unknown in chronic obstructive pulmonary disease (COPD).We assessed IgA synthesis in the lungs of COPD (n=28) and control (n=21) patients, and regulation of B-cells co-cultured with in vitro-reconstituted airway epithelium.In COPD lung tissue, synthesis of IgA1 was increased, which led to its accumulation in subepithelial areas. In vitro, the COPD bronchial epithelium imprinted normal human B-cells for increased production of IgA (mainly IgA1) and maturation into CD38 + plasma cells. These effects were associated with upregulation of TACI (transmembrane activator and CAML interactor) and were observed under resting conditions, while being partly inhibited upon stimulation with cigarette smoke extract. Interleukin (IL)-6 and BAFF (B-cell activating factor)/APRIL (a proliferation-inducing ligand) were upregulated in the COPD epithelium and lung tissue, respectively; the IgA-promoting effect of the COPD bronchial epithelium was inhibited by targeting IL-6 and, to a lower extent, by blocking TACI.These data show that in COPD, the bronchial epithelium imprints B-cells with signals promoting maturation into IgA-producing plasma cells through the action of two epithelial/B-cell axes, namely the IL-6/IL-6 receptor and BAFF-APRIL/TACI pathways, while cigarette smoke partly counteracts this IgApromoting effect. @ERSpublications COPD epithelium induces B-cell maturation of IgA-producing plasma cells via IL-6/IL-6R and BAFF-APRIL/TACI pathways

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“…Epidemiologic studies showed that cigarette smoking resulted in higher prevalence of (class-switched) memory B cells in peripheral blood and memory IgG+ B cells in the lung [70, 71]. Smokers also exhibited an elevated level of circulating IgE, leading to the potential development of atopic diseases and asthma [72].…”

Section: Effects Of Cigarette Smoking On Adaptive Immunitymentioning

confidence: 99%

Impacts of cigarette smoking on immune responsiveness: Up and down or upside down?

et al. 2016

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Cigarette smoking is associated with numerous diseases and poses a serious challenge to the current healthcare system worldwide. Smoking impacts both innate and adaptive immunity and plays dual roles in regulating immunity by either exacerbation of pathogenic immune responses or attenuation of defensive immunity. Adaptive immune cells affected by smoking mainly include T helper cells (Th1/Th2/Th17), CD4+CD25+ regulatory T cells, CD8+ T cells, B cells and memory T/B lymphocytes while innate immune cells impacted by smoking are mostly DCs, macrophages and NK cells. Complex roles of cigarette smoke have resulted in numerous diseases, including cardiovascular, respiratory and autoimmune diseases, allergies, cancers and transplant rejection etc. Although previous reviews have described the effects of smoking on various diseases and regional immunity associated with specific diseases, a comprehensive and updated review is rarely seen to demonstrate impacts of smoking on general immunity and, especially on major components of immune cells. Here, we aim to systematically and objectively review the influence of smoking on major components of both innate and adaptive immune cells, and summarize cellular and molecular mechanisms underlying effects of cigarette smoking on the immune system. The molecular pathways impacted by cigarette smoking involve NFκB, MAP kinases and histone modification. Further investigations are warranted to understand the exact mechanisms responsible for smoking-mediated immunopathology and to answer lingering questions over why cigarette smoking is always harmful rather than beneficial even though it exerts dual effects on immune responses.

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Differential switching to IgG and IgA in active smoking COPD patients and healthy controls

Cited by 39 publications

References 46 publications

Relationships between Mucosal Antibodies, Non-Typeable Haemophilus influenzae (NTHi) Infection and Airway Inflammation in COPD

Relationships between Mucosal Antibodies, Non-Typeable Haemophilus influenzae (NTHi) Infection and Airway Inflammation in COPD

Increased IgA production by B-cells in COPDvialung epithelial interleukin-6 and TACI pathways

Impacts of cigarette smoking on immune responsiveness: Up and down or upside down?

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