title: Anticitrullinated protein antibody, but not its titer, is a predictor of radiographic progression and disease activity in rheumatoid arthritis.
abstract: OBJECTIVE
  To study the contribution of anticitrullinated protein antibody (ACPA), and especially of its titer, to radiographic progression and disease activity in rheumatoid arthritis (RA).
  
  
  METHODS
  Patients with RA (n = 396) who attended a Japanese clinic within 2 years after disease onset were divided into the following groups according to second-generation (ACPA-2) ACPA titer on their first visit: negative (0-4.4 U/ml; n = 115), low-positive (4.5-121 U/ml; n = 141), and high-positive (> 121 U/ml; n = 140). The ACPA-2-positive groups were further subdivided into lowest (4.5-32 U/ml), low (33-121 U/ml), high (122-277 U/ml), and highest (> 278 U/ml) quartiles. All patients were treated with disease-modifying antirheumatic drugs (DMARD) including methotrexate, but not biologics. Subsequent radiographic progression and disease activity for 2 years were prospectively evaluated using the van der Heijde-modified Sharp score (SHS) and 28-joint Disease Activity Score (DAS28).
  
  
  RESULTS
  After treatment with DMARD, the disease activity (including number of swollen joints, number of tender joints, duration of morning stiffness, DAS28-erythrocyte sedimentation rate, and DAS28-C-reactive protein) was significantly decreased in all patient groups. Disease activity and radiographic progression as revealed by the change in SHS remained relatively higher in the ACPA-2 low- and high-positive groups as compared with the ACPA-2-negative group. The relationship between the titer of ACPA-2 at baseline and subsequent radiographic progression was not exactly linear, and the extent of disease activity or radiographic progression was similar between ACPA-2 low- and high-positive groups and also between ACPA-2 lowest- and highest-positive quartile groups. The results were demonstrable in cumulative SHS probability plots, and also repeatable in seronegative patients, which indicated that the titer of ACPA-2 is not a predictor of disease activity or radiographic progression in RA, and ACPA-2-negative patients, especially those with < 3 U/ml, showed minimal radiographic progression.
  
  
  CONCLUSIONS
  Presence of ACPA-2, but not its titer, at baseline is a predictor of radiographic progression or disease activity, where radiographic progression is minimal in ACPA-2-negative patients.
authors.affiliation: Department of Medicine, Kyushu University, Beppu Hospital, Tsurumihara, Beppu 874-0838, Japan. shiozawa@beppu.kyushu-u.ac.jp
authors.forename: Kazuko
authors.initials: K
authors.lastname: Shiozawa
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Kawasaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamane
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Yoshihara
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Kenichi
authors.initials: K
authors.lastname: Uto
authors.forename: Shunichi
authors.initials: S
authors.lastname: Shiozawa
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011859:Radiography
chemical_list: D001323:Autoantibodies; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide