RT Journal Article
SR Electronic
T1 Investigation of the citrullination pathway in the pathogenesis of fibrotic lung disorders
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P1764
VO 40
IS Suppl 56
A1 Katerina Antoniou
A1 Katerina Samara
A1 Ismini Lasithiotaki
A1 Panos Pantelidis
A1 Nikolaos Siafakas
A1 Athol Wells
YR 2012
UL http://erj.ersjournals.com/content/40/Suppl_56/P1764.abstract
AB Rationale: Our hypothesis was to explore whether an autoimmune process implicating anticitrullinated peptide immunity is implicated in pulmonary fibrosis, both idiopathic and autoimmune.Materials and Methods: We evaluated the expression of PADI2 and PADI4, the enzymes mainly catalyzing the citrullination process, in the bronchoalveolar lavage fluid (BALF) of 53 IPF patients, 37 patients with rheumatoid lung (RA-ILD) and 10 healthy controls. Survival was evaluated against smoking status, using proportional hazards analysis, adjusting for sex, age, disease severity (composite physiologic index [CPI]), and PADI2 and PADI4 levels.Results: Both PADI2 and PADI4 mRNA expression levels were increased in IPF and RA-ILD compared to controls (p<10-4). Protein expression revealed a higher expression of PADI2 and PADI4 in the RA-ILD compared to controls (p<0.005 for both proteins) and IPF (p<0.005 and p<0.05 respectively). PADI4 protein expression was also increased in IPF compared to controls (p<0.005). Finally, PADI4 mRNA expression was higher in the smokers than non-smokers (p=0.01). Multivariate analysis with stepwise logistic regression identified three factors that independently predict mortality in the study population: CPI, age and both PADI2 and PADI4 levels (examined in separate models). When both PADI2 and PADI4 were included in the same multivariate model, both were independently predictive of late mortality after adjustment for CPI, age, gender and smoking status.Conclusion: These results suggest that citrullination is an active process in both autoimmune and idiopathic lung fibrosis. The role of citrullinated enzymes as biomarkers predictive of late mortality merits further evaluation.