title: Citrullination in extra-articular manifestations of rheumatoid arthritis.
abstract: BACKGROUND
  Anti-citrullinated protein antibodies have been detected with high specificity in serum of patients with rheumatoid arthritis (RA), and citrullination of proteins may play a key role in the pathogenesis of RA. We therefore investigated the presence of citrullination in two extra-articular manifestations of RA, interstitial pneumonia (IP) and rheumatoid nodules.
  
  
  METHODS
  Open-lung biopsy specimens from patients with RA-associated IP (n = 18), idiopathic IP (n = 20) and controls (n = 10), as well as specimens of rheumatoid nodules from 26 patients, were examined. All sections were incubated with an anti-modified citrulline antibody. Masked scoring of stained sections and analysis of results by stratification according to demographic and clinical characteristics was performed.
  
  
  RESULTS
  Presence of citrulline could be detected in eight lung specimens of patients with RA-associated IP (44%) and nine patients with idiopathic IP (46%). Conversely, lung tissue from control patients showed weak extracellular citrullination in only two cases (20%). Citrullination did not show any significant associations with demographic or clinical characteristics such as age, gender, smoking habits, disease severity, histological subtype, degree of inflammation or steroid use. Rheumatoid nodules were citrulline positive in a majority of cases (70%).
  
  
  CONCLUSIONS
  Citrullination is present in extra-articular manifestations of RA such as IP and nodules. In contrast to the high specificity of anti-citrulline antibodies in RA, citrullination is not only restricted to RA but can also be observed in idiopathic IP. Whether citrullination significantly contributes to the initiation or perpetuation of autoimmunity or merely reflects ongoing inflammation remains to be clarified.
authors.affiliation: Division of Rheumatology, Mayo Clinic College of Medicine, 200 1St St SW Rochester, MN 55905, USA. Bongartz.tim@mayo.edu
authors.forename: T
authors.initials: T
authors.lastname: Bongartz
authors.forename: T
authors.initials: T
authors.lastname: Cantaert
authors.forename: S R
authors.initials: SR
authors.lastname: Atkins
authors.forename: P
authors.initials: P
authors.lastname: Harle
authors.forename: J L
authors.initials: JL
authors.lastname: Myers
authors.forename: C
authors.initials: C
authors.lastname: Turesson
authors.forename: J H
authors.initials: JH
authors.lastname: Ryu
authors.forename: D
authors.initials: D
authors.lastname: Baeten
authors.forename: E L
authors.initials: EL
authors.lastname: Matteson
mesh_terms: D000368:Aged; D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000150:complications* / Q000378:metabolism; D001706:Biopsy; D002956:Citrulline / Q000032:analysis*; D003094:Collagen; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008168:Lung / Q000737:chemistry; D017563:Lung Diseases, Interstitial / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008875:Middle Aged; D012218:Rheumatoid Nodule / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D012720:Severity of Illness Index
chemical_list: D002956:Citrulline; D003094:Collagen