title: Avidity maturation of anti-citrullinated protein antibodies in rheumatoid arthritis.
abstract: OBJECTIVE
  Anti-citrullinated protein antibodies (ACPAs) are highly specific for rheumatoid arthritis (RA) and are present years before the onset of symptoms. The avidity of autoantibodies can have a strong impact on their effector potency. This study was undertaken to analyze the avidity of ACPAs in serum samples obtained from ACPA-positive healthy individuals (predisease), patients with early disease, and patients with established RA as well as the avidity maturation over time in samples from healthy subjects who later developed RA.
  
  
  METHODS
  We measured ACPA avidity in serum samples from ACPA-positive healthy individuals, symptomatic individuals, and patients with established RA in 5 collections from The Netherlands, Canada, and Austria. We determined the dynamics of avidity maturation of ACPAs from the predisease stage to established disease in 1 case from the native North American population and in 10 cases from a Dutch blood donor cohort.
  
  
  RESULTS
  The overall ACPA response was characterized by low-avidity antibodies. Higher-avidity ACPAs were observed in symptomatic patients only, while low-avidity ACPAs were observed in both healthy subjects and patients. In longitudinal samples obtained from subjects prior to disease onset, ACPA avidity increased over time until disease onset. No further avidity maturation was observed after disease onset.
  
  
  CONCLUSIONS
  Our findings indicate that avidity maturation of the ACPA response takes place prior to disease onset.
authors: Leiden University Medical Center, Leiden, The Netherlands.
authors: P
authors: P
authors: Suwannalai
authors: L A
authors: LA
authors: van de Stadt
authors: H
authors: H
authors: Radner
authors: G
authors: G
authors: Steiner
authors: H S
authors: HS
authors: El-Gabalawy
authors: C M Jol-van der
authors: CM
authors: Zijde
authors: M J
authors: MJ
authors: van Tol
authors: D
authors: D
authors: van Schaardenburg
authors: T W J
authors: TW
authors: Huizinga
authors: R E M
authors: RE
authors: Toes
authors: L A
authors: LA
authors: Trouw
mesh_terms: D000915:Antibody Affinity / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D007117:Immunization, Secondary; D008137:Longitudinal Studies; D010456:Peptides, Cyclic / Q000276:immunology*; D013997:Time Factors
chemical_list: D001323:Autoantibodies; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide