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慢性阻塞性肺疾病患者痰和血清自身抗体的差异表达。

Differential expression of sputum and serum autoantibodies in patients with chronic obstructive pulmonary disease.

机构信息

Medical Sciences Graduate Program, McMaster University, Hamilton, Ontario, Canada.

Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada.

出版信息

Am J Physiol Lung Cell Mol Physiol. 2021 Jun 1;320(6):L1169-L1182. doi: 10.1152/ajplung.00518.2020. Epub 2021 Apr 28.

Abstract

Chronic obstructive pulmonary disease (COPD) is a complex and progressive respiratory disease. Autoimmune processes have been hypothesized to contribute to disease progression; however, the presence of autoantibodies in the serum has been variable. Given that COPD is a lung disease, we sought to investigate whether autoantibodies in sputum supernatant would better define pulmonary autoimmune processes. Matched sputum and serum samples were obtained from the Airways Disease Endotyping for Personalized Therapeutics (ADEPT) study and at the Guangzhou Institute of Respiratory Health (GIRH). Samples were collected from patients with varying severity of COPD, asymptomatic smokers, and healthy control subjects. IgG and IgM autoantibodies were detected in sputum and serum of all subjects in both cohorts using a broad-spectrum autoantigen array. No differences were observed in sputum autoantibodies between COPD and asymptomatic smokers in either cohort. In contrast, 16% of detectable sputum IgG autoantibodies were decreased in subjects with COPD compared to healthy controls in the ADEPT cohort. Compared to asymptomatic smokers, approximately 13% of detectable serum IgG and 40% of detectable serum IgM autoantibodies were differentially expressed in GIRH COPD subjects. Of the differentially expressed specificities, anti-nuclear autoantibodies were predominately decreased. A weak correlation between increased serum IgM anti-tissue autoantibodies and a measure of airspace enlargement was observed. The differential expression of specificities varied between the cohorts. In closing, using a comprehensive autoantibody array, we demonstrate that autoantibodies are present in subjects with COPD, asymptomatic smokers, and healthy controls. Cohorts displayed high levels of heterogeneity, precluding the utilization of autoantibodies for diagnostic purposes.

摘要

慢性阻塞性肺疾病(COPD)是一种复杂且进展性的呼吸系统疾病。自身免疫过程被认为与疾病进展有关;然而,血清中的自身抗体存在差异。鉴于 COPD 是一种肺部疾病,我们试图研究痰上清液中的自身抗体是否能更好地定义肺部自身免疫过程。在 Airways Disease Endotyping for Personalized Therapeutics(ADEPT)研究和广州呼吸健康研究所(GIRH)中,从不同严重程度的 COPD 患者、无症状吸烟者和健康对照者中获得了匹配的痰和血清样本。使用广谱自身抗原阵列检测了两个队列中所有受试者的痰和血清中的 IgG 和 IgM 自身抗体。在两个队列中,COPD 患者与无症状吸烟者的痰自身抗体均无差异。相比之下,在 ADEPT 队列中,与健康对照组相比,16%的可检测痰 IgG 自身抗体在 COPD 患者中减少。与无症状吸烟者相比,在 GIRH COPD 患者中,大约 13%的可检测血清 IgG 和 40%的可检测血清 IgM 自身抗体存在差异表达。在差异表达的特异性中,抗核自身抗体主要减少。观察到血清 IgM 抗组织自身抗体增加与气道扩张程度的一个指标之间存在弱相关性。特异性的差异表达在队列之间有所不同。总之,我们使用综合自身抗体阵列证明,自身抗体存在于 COPD 患者、无症状吸烟者和健康对照者中。队列表现出高度的异质性,排除了将自身抗体用于诊断目的的可能性。

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