Chronic Obstructive Pulmonary Disease: Evidence for an Autoimmune Component

Abstract

Chronic obstructive pulmonary disease (COPD) is characterized by an irreversible limitation on pulmonary airflow associated with chronic inflammation and mucous hypersecretion (chronic bronchitis) and/or the pathological destruction of alveolar airspaces leading to emphysema. COPD, predominantly as a result of tobacco smoke exposure, represents the fourth leading cause of mortality worldwide and its prevalence is increasing. Despite this, much of the basic mechanisms which contribute to disease progression remain to be elucidated and current therapeutic approaches are, for the most part, based upon alleviating patient symptoms (bronchodilators) as opposed to treating the underlying pathological mechanisms triggered in response to cigarette smoke exposure. The classic disease paradigm suggests that an imbalance of pulmonary matrix proteases versus anti-proteases underlies the tissue destruction and inflammation associated with COPD. However, there is a growing appreciation of the complex and multifaceted nature of the pathological mechanisms associated with disease progression. Recently, there has been mounting evidence indicating that COPD patients exhibit many of the characteristics of a classical autoimmune response. We will discuss current evidence in support of this paradigm and outline how future therapeutic approaches may be tailored to address this. Cellular & Molecular Immunology. 2009;6(2):81-86.

Role of increased CD8/CD28null T cells and alternative co-stimulatory molecules in chronic obstructive pulmonary disease

“…While there may be a direct pathogenic role for certain altered proteins, an indirect role via the recognition of altered self-antigens could plausibly be a mechanism of much broader relevance, as this would not depend directly on the functionality of altered proteins. Evidence for an autoimmune component of COPD has been presented by several groups [4][5][6][7]. In support of this, our group has reported increased production of T helper type 1 (Th1) proinflammatory cytokines interferon (IFN)-g and tumour necrosis factor (TNF)-a by CD8 + T cells in peripheral blood in COPD [8].…”

Airway limitation and exercise intolerance in well-regulated myasthenia gravis patients

“…Recently, there has been mounting evidence indicating that obstructive pulmonary disorder is a disease with a strong autoimmune feature (36,37). It is possible that repetitive infections trigger the immune system to react with hyper-reactivity and hence airway limitation.…”

Antielastin B-cell and T-cell immunity in patients with chronic obstructive pulmonary disease

“…The increasing presence of CD8 cells, CD4 cells and B cells in the small airways and lung tissue of patients with more severe disease,6–8 their oligoclonal aspect,8 9 and their structural organisation as tertiary lymphoid tissue10 indicate that antigen-specific stimuli elicit an immune reaction, potentially enhancing the ongoing inflammation. At present, the nature of the antigens towards which the immune response might be directed remains unclear 1 3…”