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

Abstract

Rationale Antielastin autoimmunity has been hypothesised to drive disease progression in chronic obstructive pulmonary disease (COPD). The proposed mechanism is currently disputed by conflicting data. The authors aimed to explore antibody responses against elastin in a large and extensively characterised COPD population and to assess elastin-specific peripheral T-cell reactivity in a representative subgroup. Methods Antielastin antibodies were analysed with indirect ELISA on the plasma of 320 patients with COPD (Global Initiative for Chronic Obstructive Lung Disease 1e4) and 143 smoking controls. In a second group of 40 patients with COPD and smoking controls, T-cell responses against extracellular matrix (elastin, collagen I and collagen V) were determined with enzyme-linked immunosorbent spot (EliSpot) (interferon g (IFNg) and interleukin-2) on peripheral blood mononuclear cells and compared with the responses of 11 never-smoking controls. Results Antielastin antibody titres were not elevated in patients with COPD compared with smoking controls and even decreased significantly with increasing severity of COPD (p<0.001). Lower antielastin antibody titres were also found in a subgroup of patients with CT-proven emphysema. Elastin-specific INFg-mediated T helper 1 responses could not be revealed in smoking subjects with and without COPD. Collagen I-mediated T-cell responses were also absent, which contrasted with a significant increased anticollagen V response in the smoking controls and patients with COPD compared with the never smokers (p¼0.008). Collagen V-mediated T-cell responses could not discriminate between patients with COPD and smoking controls. Conclusion A systemic immune response against elastin could not be identified in patients with COPD. By contrast, collagen V-mediated autoimmunity was increased in the subgroup of smokers and may potentially contribute to the pathogenesis of COPD.

Thorax: the Cappuccino years

“…Potentially new CT based measures49 might provide a fresh and important perspective as might novel blood and urine biomarkers 50 51. Previously promising markers of disease have had a bad year: Rinaldi et al 52 failed to confirm a previous finding of anti-elastin antibodies in COPD although blood and urine desmosine, an elastin degradation product, has emerged as a promising biomarker 51. We suspect that the future is to view these measures as risk factors rather than arbitrary defining characteristics, as has been cogently pointed out by Guy Marks in a ‘must read’ opinion article 48.…”

Microbiota Promotes Chronic Pulmonary Inflammation by Enhancing IL-17A and Autoantibodies

“…However self-antigens derived from the collateral damage of the lung tissue might also be presented within LFs and result in the production of autoantibodies (22,64). While sequence analysis of B cell clones isolated from LFs in COPD lungs has indicated the presence of an oligoclonal, antigen specific humoral response (25), there are conflicting reports regarding the production of self-reactive antibodies (28)(29)(30)(31)(32). It is important to note that most of these studies assess systemic antibody levels, which may not be representative of responses within the lung.…”

A study of chronic obstructive pulmonary disease-specific causes of osteoporosis with emphasis on the emphysema phenotype

“…However, several studies could not identify antielastin antibodies or their levels in plasma or bronchoalveolar lavage were not elevated compared to controls. [434445] The review and its references cite the osteoporosis of rheumatoid arthritis, lupus, and celiac disease as conditions where auto-antibodies have been “associated” with low BMD. [16] Even in these exclusively autoimmune conditions, osteoporosis is multifactorial as there exist no antibodies directed against bone tissue.…”