Smoking is associated with increased levels of extracellular peptidylarginine deiminase 2 (PAD2) in the lungs
| Autor: | Damgaard D, Friberg Bruun Nielsen M, Quisgaard Gaunsbaek M, Yaseelan Palarasah, Svane-Knudsen V, Ch, Nielsen |
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| Zdroj: | Europe PubMed Central Scopus-Elsevier Damgaard, D, Friberg Bruun Nielsen, M, Quisgaard Gaunsbaek, M, Palarasah, Y, Svane-Knudsen, V & Nielsen, C H 2015, ' Smoking is associated with increased levels of extracellular peptidylarginine deiminase 2 (PAD2) in the lungs ', Clinical and Experimental Rheumatology, vol. 33, no. 3, pp. 405-408 . |
| Popis: | OBJECTIVES: Smoking is a well-established risk factor in rheumatoid arthritis (RA), and citrullination of self-antigens 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 cell-free 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).CONCLUSIONS: 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. |
| Databáze: | OpenAIRE |
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