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

1, 2, 3, 4, 5, 6

 

  1. Institute for Inflammation Research, Department of Infectious Diseases and Rheumatology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
  2. Institute for Inflammation Research, Department of Infectious Diseases and Rheumatology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
  3. Department of ENT surgery, Odense University Hospital, Odense, Denmark.
  4. Institute for Inflammation Research, Department of Infectious Diseases and Rheumatology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
  5. Department of ENT surgery, Odense University Hospital, Odense, Denmark.
  6. Institute for Inflammation Research, Department of Infectious Diseases and Rheumatology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.

CER7795
2015 Vol.33, N°3
PI 0405, PF 0408
Brief Papers

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PMID: 25897949 [PubMed]

Received: 29/07/2014
Accepted : 23/01/2015
In Press: 16/04/2015
Published: 22/06/2015

Abstract

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.

Rheumatology Article