Abstract
Objective. Smoking is a well-established risk factor in rheumatoid arthritis (RA), and citrullination of selfantigens plays a pathogenic role in the majority of patients. Increased numbers of peptidylarginine deiminase 2 (PAD2)-containing macrophages have been demonstrated in bronchoalveolar lavage (BAL) fluid from smokers, but intracellularly located PAD cannot be responsible for citrullination of extracellular self-antigens. We aimed to establish a link between smoking and extracellular PAD2 in the lungs. Methods. BAL fluid samples were obtained from 13 smokers and 11 nonsmoking controls. Total protein content and C-reactive protein (CRP) concentration were determined after separating cells from the samples. PAD2 content in cell-free BAL fluids was measured by means of a PAD2-specific sandwich ELISA. Results. Significantly increased levels of soluble PAD2 were detected in cellfree BAL fluids from smokers as compared to non-smokers (p=0.018). The PAD2 content correlated with the overall CRP levels (p=0.009) and cell count (p=0.016). Conclusion. This first demonstration of increased levels of extracellular PAD2 in the lungs of smokers supports the hypothesis that smoking promotes extracellular citrullination of proteins. This may represent a pathological event upstream for the production of anti-citrullinated protein antibodies (ACPAs) among RA patients carrying HLA-molecules capable of binding citrullinated self-peptides.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Clinical and Experimental Rheumatology |
| Vol/bind | 33 |
| Udgave nummer | 3 |
| Sider (fra-til) | 405-8 |
| Antal sider | 4 |
| ISSN | 0392-856X |
| Status | Udgivet - 2015 |
| Udgivet eksternt | Ja |