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Ann Rheum Dis. 2014 Aug;73(8):1487-94. doi: 10.1136/annrheumdis-2012-203160. Epub 2013 May 28.

Association of fine specificity and repertoire expansion of anticitrullinated peptide antibodies with rheumatoid arthritis associated interstitial lung disease.

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  • 1Division of Rheumatology, Columbia University, College of Physicians and Surgeons, New York, New York, USA.
  • 2Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
  • 3Veterans Administration Palo Alto Health Care System, Palo Alto, California, USA Division of Rheumatology, Stanford University, Stanford, California, USA.
  • 4Division of Pulmonary and Critical Care Medicine, Yale University, New Haven, Connecticut, USA.



Interstitial lung disease (ILD) is associated with high morbidity and mortality in rheumatoid arthritis (RA). Citrullinated proteins are observed in RA lung tissues; however, the association of specific anticitrullinated peptide antibodies (ACPA) with ILD in RA is unknown.


RA patients underwent multidetector CT (MDCT) of the chest, from which ILD features and a semiquantitative ILD Score (ILDS; range 0-32) were assessed. Anti-CCP (CCP2) and levels of a panel of antibodies against 17 citrullinated and four non-citrullinated peptides were assessed from concurrent serum samples using a custom Bio-Plex bead array. High level ACPA was defined as ≥the group 75th percentile.


Among the 177 RA patients studied, median levels of CCP2 and all specific ACPAs were 46-273% higher among RA patients with versus those without ILD (all p values <0.05), and higher levels correlated with higher ILDS. In contrast, levels of non-citrullinated protein antibodies were not higher in those with ILD. RA patients had a median of 2 high level ACPA reactivities (range 0-16), with each high level ACPA associated, on average, with a 0.10 unit higher ILDS (p=0.001). This association remained significant after adjusting for characteristics associated with ILD (age, gender, current and former smoking, Disease Activity Score for 28 joints, current prednisone and leflunomide use). More high level ACPA were observed in those with versus without pulmonary function restriction or impaired diffusion.


Our findings of a broader ACPA repertoire in RA ILD suggest a possible role for ACPA in the pathogenesis of ILD.

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Ant-CCP; Autoantibodies; Rheumatoid Arthritis

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