title: Citrulline dependence of anti-cyclic citrullinated peptide antibodies in systemic lupus erythematosus as a marker of deforming/erosive arthritis.
abstract: OBJECTIVE
  Anti-cyclic citrullinated peptide (CCP) antibodies are a serological marker for rheumatoid arthritis (RA); up to 10%-15% of patients with systemic lupus erythematosus (SLE) are also positive. While anti-CCP in RA is citrulline-dependent, anti-CCP in some other diseases is citrulline-independent and reacts with both CCP and the unmodified (arginine-containing) cyclic arginine peptide (CAP). We investigated the citrulline dependence of anti-CCP and its significance in the arthritis of SLE.
  
  
  METHODS
  IgG anti-CCP was compared by ELISA to anti-CAP in sera from patients with SLE (n = 335) and RA (n = 47) and healthy controls (n = 35). SLE patients were divided into 5 groups based on their joint involvement: subset I: deforming/erosive arthritis (n = 20); II: arthritis fulfilling (or likely fulfilling) American College of Rheumatology criteria for RA but without erosions (n = 18); III: joint swelling but not fulfilling RA criteria (n = 39); IV: arthritis without documented joint swelling (n = 194); and V: no arthritis (n = 58).
  
  
  RESULTS
  Anti-CCP (> 1.7 units) was found in 68% (32/47) of patients with RA and 17% (55/329) of those with SLE. It was more common in SLE patients with deforming/erosive arthritis (38%). High anti-CCP (> 10 units) was found in RA (26%) and deforming/erosive SLE (12%). High anti-CCP/CAP ratios (> 2, indicating a selectivity to CCP) were found in 91% of anti-CCP-positive RA and 50% of anti-CCP-positive SLE patients with deforming/erosive arthritis. Patients from subset II did not have high anti-CCP/CAP.
  
  
  CONCLUSIONS
  Citrulline dependence or high levels (> 10) of anti-CCP were common in SLE patients with deforming/erosive arthritis, while most anti-CCP in SLE patients was citrulline-independent. This may be useful in identifying a subset of SLE patients with high risk for development of deforming/erosive arthritis.
authors.affiliation: Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Florida, Gainesville, Florida 32610-0221, USA.
authors.forename: Prasanthi
authors.initials: P
authors.lastname: Kakumanu
authors.forename: Eric S
authors.initials: ES
authors.lastname: Sobel
authors.forename: Sonali
authors.initials: S
authors.lastname: Narain
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Akaogi
authors.forename: Yoshioki
authors.initials: Y
authors.lastname: Yamasaki
authors.forename: Mark S
authors.initials: MS
authors.lastname: Segal
authors.forename: Paulette C
authors.initials: PC
authors.lastname: Hahn
authors.forename: Edward K L
authors.initials: EK
authors.lastname: Chan
authors.forename: Westley H
authors.initials: WH
authors.lastname: Reeves
authors.forename: Minoru
authors.initials: M
authors.lastname: Satoh
mesh_terms: D001172:Arthritis, Rheumatoid / Q000097:blood / Q000276:immunology / Q000473:pathology; D044466:Asian People; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D002956:Citrulline / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007596:Joints / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000145:classification / Q000276:immunology* / Q000473:pathology*; D010456:Peptides, Cyclic / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D002956:Citrulline