Background: Increased protein citrullination and peptidylarginine deiminases (PADIs), which catalyze the citrullination
process, are central in Rheumatoid arthritis pathogenesis and probably involved in the initial steps towards autoimmunity.
Approximately, 10% of RA patients develop clinically significantly ILD. A possible shared role of protein citrullination in
rheumatoid arthritis associated interstitial lung disease (RA-ILD), and idiopathic pulmonary fibrosis (IPF) pathogenesis
remains unclear.
Methods: We evaluated PADI2 and PADI4 mRNA expression in bronchoalveolar lavage fluid (BALF) cells of 59 patients with
IPF, 27 patients RA-ILD and 10 healthy controls. PADI 2 and 4 expression was analyzed by western blot and
immunohistochemistry. Citrullinated protein levels were also quantified.
Results: PADI4 mRNA and protein levels were higher in RA-ILD and IPF than controls. Furthermore, PADI4 mRNA levels
showed an increase among smokers in RA-ILD. PADI4 expression was detected in granulocytes and macrophages in all
groups, with the strongest cytoplasmic expression observed in granulocytes in RA-ILD and IPF. PADI2 mRNA and
immunostaining of BAL cells, were similar in all groups among smokers. Overall, stronger staining was observed in current
smokers. Citrullinated peptides were significantly increased in IPF compared to RA-ILD and controls. In RA-ILD, protein
citrullination strongly correlated with PADI4 expression and anti-citrullinated protein antibodies (ACPAs).
Conclusions: These results suggest that the citrullination pathway is upregulated in IPF and in RA-ILD.