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.
| Original language | English |
|---|---|
| Journal | Clinical and Experimental Rheumatology |
| Volume | 33 |
| Issue number | 3 |
| Pages (from-to) | 405-8 |
| Number of pages | 4 |
| ISSN | 0392-856X |
| Publication status | Published - 2015 |
| Externally published | Yes |
Keywords
- Aged
- Biomarkers
- Bronchoalveolar Lavage Fluid
- C-Reactive Protein
- Case-Control Studies
- Enzyme-Linked Immunosorbent Assay
- Female
- Forced Expiratory Volume
- Humans
- Hydrolases
- Lung
- Male
- Middle Aged
- Smoking
- Up-Regulation
- Vital Capacity