Homocitrullination May Be Linked to Interstitial Lung Disease in Rheumatoid Arthritis

xray image of pneumonia and a hand with rheumatoid arthritis
A link between homocitrullination and the development of interstitial lung disease in patients with rheumatoid arthritis may exist.

A link between homocitrullination and the development of interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA) may exist, according to the results of a cross-sectional study published in the Annals of the Rheumatic Diseases.

RA-associated ILD (RA-ILD) is associated with high mortality, therefore early detection is necessary for establishing an individualized treatment strategy in these patients.  Anti-carbamylated protein antibodies (Anti-CarP) are associated with poor disease outcomes in patients with RA and have been detected in various chronic lung diseases regardless of RA history. Thus, researchers analyzed the association between Anti-CarP and ILD in RA patients.

A total 179 patients were enrolled in the study; 37 (21%) of whom were diagnosed with RA-ILD. The researchers found that Anti-CarP specificities were more frequent in patients with RA-ILD. Anti-CarP specificities showed a robust effect towards increasing the odds of ILD in a multivariate analysis. In addition, serum titers of Anti-CarP were significantly higher in patients with RA-ILD and The researchers also observed similar findings in the replication sample.

This is the first time that an association between RA-ILD and Anti-CarP was demonstrated, independent of smoking, sex, age, RA disease duration, anticitrullinated protein antibody, and rheumatoid factor. 

It is important to note that this study had several limitations: a relatively small proportion of patients with RA-ILD was included and treatment and disease activity were not included. Additionally, most patients were of Mediterranean Caucasian origin, which has been associated with a less aggressive RA course and a lower prevalence of extra-articular disease.

Related Articles

“In conclusion, a robust association between different Anti-CarP and RA-ILD was found after adjusting for multiple confounders,” the researchers stated. “These findings pose the debate whether a link between homocitrullination and the development of this devastating extra-articular manifestation exists.” However, these results should be interpreted with caution and further studies are needed.


Castellanos-Moreira R, Rodríguez-García SC, Gomara MJ, et al. Anti-carbamylated proteins antibody repertoire in rheumatoid arthritis: evidence of a new autoantibody linked to interstitial lung disease [published online March 10, 2020]. Ann Rheum Dis. doi:10.1136/annrheumdis-2019-216709