Staples Karl J, Taylor Stephen, Thomas Steve, Leung Stephanie, Cox Karen, Pascal Thierry G, Ostridge Kristoffer, Welch Lindsay, Tuck Andrew C, Clarke Stuart C, Gorringe Andrew, Wilkinson Tom M A
Clinical & Experimental Sciences, University of Southampton Faculty of Medicine, Southampton General Hospital, Tremona Road, Southampton, United Kingdom.
Wessex Investigational Sciences Hub, University of Southampton Faculty of Medicine, Southampton General Hospital, Tremona Road, Southampton, United Kingdom.
PLoS One. 2016 Nov 29;11(11):e0167250. doi: 10.1371/journal.pone.0167250. eCollection 2016.
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.
不可分型流感嗜血杆菌（NTHi）是慢性阻塞性肺疾病（COPD）的关键病原体，与气道炎症和病情加重风险相关。目前尚不清楚为何有些患者易受其定植。我们推测这种易感性可能是由于黏膜体液免疫缺陷所致。我们研究（NCT01701869）的目的是量化肺部针对NTHi的抗体数量和特异性，以及健康人群和COPD患者中与之相关的感染和炎症风险。对24例轻至中度COPD患者及8例年龄和吸烟情况相匹配的对照者进行了静脉采血、痰液诱导和支气管镜检查。与对照组相比，COPD患者支气管肺泡灌洗（BAL）液中总IgG1、IgG2、IgG3、IgM和IgA浓度显著升高。7例COPD患者的肺部检测到NTHi（NTHi阳性，占29%），这些患者既往病情加重的中位数次数高于NTHi阴性患者，且有全身炎症增加的证据。比较NTHi阳性和阴性患者时，我们观察到NTHi阳性患者BAL液中总IgG1（p = 0.0068）和NTHi特异性IgG1（p = 0.0433）的量均减少，但总IgA或IgM无差异。我们未观察到NTHi阳性患者血清中IgG1减少的证据，表明这种现象仅限于气道。此外，NTHi阳性患者BAL液中IL-1β水平显著高于NTHi阴性的COPD患者（p = 0.0003）。本研究表明，NTHi的存在与NTHi定植的COPD患者气道中IgG1水平降低及其功能受损有关。总IgG1和NTHi特异性IgG1的这种降低与更严重的全身和气道炎症以及更频繁的病情加重病史相关，这可能解释了一些COPD患者对NTHi影响的易感性。
Hum Vaccin Immunother. 2024-12-31
Front Immunol. 2018-11-5
Int J Chron Obstruct Pulmon Dis. 2011-6-16
J Allergy Clin Immunol. 2012-11-8
Hum Vaccin Immunother. 2024-12-31
Front Immunol. 2022
Acta Biochim Biophys Sin (Shanghai). 2022-1-25
Am J Respir Crit Care Med. 2016-3-15
Mucosal Immunol. 2015-7
Eur Respir J. 2014-12-23
Genome Med. 2014-11-20
Zotero 插件
