Smoking is associated with increased levels of extracellular peptidylarginine deiminase 2 (PAD2) in the lungs

Dres Damgaard, Michael Friberg Bruun Nielsen, Maria Quisgaard Gaunsbaek, Yaseelan Palarasah, Viggo Svane-Knudsen, Claus Henrik Nielsen

Research output: Contribution to journalJournal articleResearchpeer-review


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.

Original languageEnglish
JournalClinical and Experimental Rheumatology
Issue number3
Pages (from-to)405-408
Publication statusPublished - 16. Apr 2015


  • Bronchoalveolar lavage
  • Peptidylarginine deiminase
  • Rheumatoid arthritis
  • Smoking


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