title: Association of fine specificity and repertoire expansion of anticitrullinated peptide antibodies with rheumatoid arthritis associated interstitial lung disease.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Our findings of a broader ACPA repertoire in RA ILD suggest a possible role for ACPA in the pathogenesis of ILD.
authors.affiliation: Division of Rheumatology, Columbia University, College of Physicians and Surgeons, New York, New York, USA.
authors.forename: Jon T
authors.initials: JT
authors.lastname: Giles
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Sonye K
authors.initials: SK
authors.lastname: Danoff
authors.affiliation: Veterans Administration Palo Alto Health Care System, Palo Alto, California, USA Division of Rheumatology, Stanford University, Stanford, California, USA.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Sokolove
authors.affiliation: Veterans Administration Palo Alto Health Care System, Palo Alto, California, USA Division of Rheumatology, Stanford University, Stanford, California, USA.
authors.forename: Catriona A
authors.initials: CA
authors.lastname: Wagner
authors.affiliation: Division of Rheumatology, Columbia University, College of Physicians and Surgeons, New York, New York, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Winchester
authors.affiliation: Division of Rheumatology, Columbia University, College of Physicians and Surgeons, New York, New York, USA.
authors.forename: Dimitrios A
authors.initials: DA
authors.lastname: Pappas
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Stanley
authors.initials: S
authors.lastname: Siegelman
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Yale University, New Haven, Connecticut, USA.
authors.forename: Geoff
authors.initials: G
authors.lastname: Connors
authors.affiliation: Veterans Administration Palo Alto Health Care System, Palo Alto, California, USA Division of Rheumatology, Stanford University, Stanford, California, USA.
authors.forename: William H
authors.initials: WH
authors.lastname: Robinson
authors.affiliation: Division of Rheumatology, Columbia University, College of Physicians and Surgeons, New York, New York, USA.
authors.forename: Joan M
authors.initials: JM
authors.lastname: Bathon
mesh_terms: D000368:Aged; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000276:immunology* / Q000401:mortality; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D008168:Lung / Q000000981:diagnostic imaging / Q000276:immunology; D017563:Lung Diseases, Interstitial / Q000209:etiology / Q000276:immunology* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009017:Morbidity; D010456:Peptides, Cyclic / Q000097:blood*; D011446:Prospective Studies; D012307:Risk Factors; D012680:Sensitivity and Specificity; D014057:Tomography, X-Ray Computed
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide
keywords: Ant-CCP; Autoantibodies; Rheumatoid Arthritis