Journal Article

Auto-antibodies against carbonyl-modified vimentin in COPD: potential role as a biomarker

Adcock, I., Caramori, G., Chung, K. F, Lollinga, W., Kirkham, P. A., Hylkema, M. N., Heinemann, L., Papi, A.

2025

Overview

COPD has many hallmarks of autoimmune dysfunction. Driving this autoimmune response are self-antigens, such as highly abundant structural proteins and cellular proteins, which can lead to the production of auto-antibodies. However, controversy surrounds the detection of some of these auto-antibodies as they have often been screened against native, unmodified proteins. Autoantigens arise as a result of a conformational change in the native protein exposing hidden epitopes or by the creation of neo-epitopes through chemical or enzymatic modifications, often caused by oxidative/carbonyl stress. In this study, we screened for auto-antibodies targeting key structural proteins modified by oxidative/carbonyl stress in peripheral blood from stable COPD patients versus control subjects using ELISA. We found an auto-antibody response against unmodified, carbonyl-modified and citrinylated vimentin, with the highest response observed against carbonyl-modified vimentin. Both the IgG and IgM antibody titres against carbonyl-modified were significantly increased in COPD patients compared to healthy non-smokers. Smokers also displayed increased antibody levels against carbonyl-modified vimentin, but only for the IgG isotype. Selectivity analysis indicated that 70% and 63% of COPD patients had higher IgM and IgG titres, respectively, compared to non-smokers. In contrast only 26% and 48% of smokers had higher IgM and IgG titres, respectively, than non-smokers. ROC analysis gave AUC values of 0.78 ( p  < 0.01) and 0.84 ( p  < 0.001) for IgM and IgG, respectively, for COPD versus non-smokers, which fell to 0.70 ( p  < 0.01) and 0.64 (NS), respectively, when asymptomatic smokers were included. No significant increase in antibody titre against carbonyl-modified elastin or collagen was observed in COPD patients or asymptomatic smokers. We conclude that IgM autoantibody responses against carbonyl modified vimentin could serve as a simple blood-based biomarker for COPD, reflecting the disease's pathophysiology, and could help in patient stratification and diagnosis.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Allergology / Analysis / Antibodies / Antibody response / Antigenic determinants / Antigens / Autoantibodies / Autoantigens / Autoimmunity / B cells / Biomarker / Biomarkers / Biomedical and Life Sciences / Biomedicine / Bronchodilators / Carbonyl / Carbonyl compounds / Chronic obstructive pulmonary disease / Collagen / Cytokines and Growth Factors / Development and progression / Elastin / Enzyme-linked immunosorbent assay / Epitopes / Extracellular matrix / Gastroenterology / Immune response / Immunoglobulin G / Immunoglobulin M / Immunology / Lung diseases, Obstructive / Oxidative stress / Peripheral blood / Pharmacology/Toxicology / Proteins / Respiratory / Rheumatology / Smoking / Structural proteins / Tobacco smoke / Vimentin