Autoimmunity and COPD

Abstract

COPD is a leading cause of morbidity and mortality worldwide. Long-term cigarette smoking is the cause of > 90% of COPD cases in Westernized countries. However, only a fraction of chronic heavy smokers develop symptomatic COPD by age 80. COPD is characterized by an abnormal immune response in the lower airways, and its progression is associated with infiltration of the lung by innate and adaptive inflammatory immune cells that form lymphoid follicles. There is growing evidence that both cellular- and antibody-mediated autoimmunity has a fundamental role in the pathogenesis of stable COPD. In particular, carbonyl-modified proteins may help to drive autoimmunity in COPD and cause the characteristic small airways abnormalities and even contribute to the pathogenesis of pulmonary emphysema. Although direct, indirect, and circumstantial evidence of a role for autoimmunity in stable patients with COPD has been identified, no cause-and-effect relationship between autoimmunity and the mechanisms of COPD has been firmly established in man. As such, the potential contribution of an autoimmune response to the pathogenesis of COPD exacerbation is still being investigated and represents an area of active research. Many drugs targeting autoimmune responses are already available, and the results of controlled clinical trials are awaited with great interest. The potential for measuring specific serum autoantibodies as biomarkers to predict clinical phenotypes or progression of stable COPD is promising.

Oxidative Stress in Ozone-Induced Chronic Lung Inflammation and Emphysema: A Facet of Chronic Obstructive Pulmonary Disease

“…Various pathological pathways have been proposed including increased apoptosis mechanisms ( 17 , 18 ) in addition to inflammageing and autoimmunity ( 19 ). There is growing evidence that COPD may represent a cellular senescence program associated with secretion of pro-inflammatory cytokines that cause chronic inflammation, that leads to the increased levels of reactive oxygen species that can induce oxidative stress ( 20 ).…”

“…An increasing body of evidence has been accumulating linking COPD with the process of autoimmunity, with the presence of autoantibodies in the sera of COPD patients, and with some of the antibodies correlating with particular disease phenotypes ( 19 ). Thus, it has been proposed that autoimmunity may play an important role in the pathogenesis of COPD.…”

<p>How Do Innate Immune Cells Contribute to Airway Remodeling in COPD Progression?</p>

“…In the lungs of patients with COPD, when CD8 + T cells are excessively activated, an increase in the blood CD8 + /CD4 + ratio indicates the progression of airflow limitation. 79 The CD4 + T cells in COPD mainly facilitate the functions of B cells and CD8 + T cells in the lungs, thereby both amplifying and prolonging the inflammatory response in the lung microenvironment. The Tregs in the lung maintain immune tolerance.…”

Levels of CD4+ CD25+ T Regulatory Cells in Bronchial Mucosa and Peripheral Blood of Chronic Obstructive Pulmonary Disease Indicate Involvement of Autoimmunity Mechanisms

“…However, the study included only moderate COPD patients. This is important because the prevalence of lymphoid follicles increases sharply from 25% to 30% in severe and very severe COPD for unclear reasons [17]. The progression from moderate to severe COPD, which is associated with a sharp increase in the number of follicles, may arise from a failure of regulatory mechanisms to suppress autoimmunity.…”