Lung Citrulline Levels Among Smokers May Be Linked to Rheumatoid Arthritis

Lung Citrulline Levels Among Smokers May Be Linked to Rheumatoid Arthritis

A team of researchers for the University of Oxford found an increase in citrullinated proteins in COPD, suggesting that citrullination in the lungs of smokers is mainly due to inflammation. However, besides the lungs, the researchers also found citrullination of vimentin in other organ tissues, thus suggesting that the relationship between smoking and autoimmunity in Rheumatoid Arthritis is of a complex nature.

The study entitled “Expression of citrulline and homocitrulline residues in the lungs of non-smokers and smokers: implications for autoimmunity in rheumatoid arthritis, was recently published in the journal Arthritis Research & Therapy.

Smoking is a risk factor for rheumatoid arthritis (RA), and it has been suggested that smoking-induced citrullination reduces one’s immune system response. Rheumatoid arthritis (RA) is an autoimmune disorder caused by anti-citrullinated peptide/protein antibodies (ACPA). Evidence also shows that ACPA are strongly associated with smoking, and antibodies to citrullinated α-enolase peptide 1 (CEP-1) and citrullinated vimentin, suggesting that citrullinated enolase and vimentin in the lungs play a key role in the autoantibody response. Smoke inhalation is thought to increase the levels of PADs, leading to formation of citrullinated proteins thus, driving ACPA response.

To further examine this mechanism, Patrick Venables from the Kennedy Institute of Rheumatology, University of Oxford, United Kingdom, analysed lung tissues from 10 never smokers, 10 smokers without airflow limitation, 13 COPD smokers and 8 COPD ex-smokers, and control tissue samples. Then the team of researchers examined citrullinated proteins and the deiminating enzymes peptidylarginine deiminase type-2 (PAD2) and -4 (PAD4) in the tissue samples.

Results revealed that all lung tissue samples had PAD2 and PAD4, however those with COPD had an increase in the levels of citrullination, with a minimal difference between smokers and non-smokers. Additionally, the researchers found lower levels of citrullination in tissues from other organs, principally in lymph nodes, the kidneys and skeletal muscle. Moreover, the analysis showed that Vimentin was citrullinated in non-smokers and smokers both with and without COPD.

With these results, the team of researchers indicate that vimentin, a well established autoantigen in RA, presents an increase in citrullination, both in smokers and non-smokers, thus suggesting that citrullination in the lungs of smokers is mainly due to inflammation. The researchers concluded that the ubiquity of citrullination of vimentin in the lungs and other tissues indicated that the relationship between smoking and autoimmunity in RA remains complex.

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