title: Low-avidity anticitrullinated protein antibodies (ACPA) are associated with a higher rate of joint destruction in rheumatoid arthritis.
abstract: OBJECTIVE
  Anticitrullinated protein antibodies (ACPA) are specific for rheumatoid arthritis (RA) and have been implicated in disease pathogenesis. Previously we have shown that ACPA display a considerably lower avidity as compared with antibodies against recall antigens. Nonetheless, ACPA-avidity did vary between patients. As antibody mediated effects are influenced by antibody-avidity, we now investigated ACPA-avidity in relation to biological activity and clinical outcome.
  
  
  METHODS
  We determined the avidity of ACPA and related this with severity of joint damage in two Dutch early-RA cohorts containing 199 and 132 patients respectively. Differences in effector functions of low- and high-avidity ACPA were studied.
  
  
  RESULTS
  Extensive variation in ACPA-avidity between patients was observed. This allowed the analysis of the relationship between avidity and severity. The presence of low-avidity ACPA is associated with a higher rate of joint destruction. This finding was replicated in an independent cohort. Analysis of the properties of low-versus high-avidity ACPA revealed that low-avidity ACPA are less hampered in their ability to bind 'new' citrullinated antigens. Although no differences could be observed regarding cellular activation via Fc-γ receptors, low-avidity ACPA were more potent in activating the complement system.
  
  
  CONCLUSIONS
  Patients with low-avidity ACPA display a higher rate of joint destruction. Low-avidity ACPA display a higher potency to interact with more citrullinated antigens in time and show that low-avidity ACPA are more potent in complement activation. These data indicate that (low) avidity impacts on the biological activity of ACPA and associates with a worse radiological outcome.
authors: Department of Rheumatology, Leiden University Medical Center, , Leiden, The Netherlands.
authors: Parawee
authors: P
authors: Suwannalai
authors: Karin
authors: K
authors: Britsemmer
authors: Rachel
authors: R
authors: Knevel
authors: Hans Ulrich
authors: HU
authors: Scherer
authors: E W Nivine
authors: EW
authors: Levarht
authors: Annette H
authors: AH
authors: van der Helm-van Mil
authors: Dirkjan
authors: D
authors: van Schaardenburg
authors: Tom W J
authors: TW
authors: Huizinga
authors: René E M
authors: RE
authors: Toes
authors: L A
authors: LA
authors: Trouw
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000915:Antibody Affinity / Q000276:immunology; D000941:Antigens / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging* / Q000276:immunology*; D001175:Arthrography; D015331:Cohort Studies; D003165:Complement System Proteins / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007596:Joints / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology*; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D000941:Antigens; D000939:Epitopes; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D003165:Complement System Proteins
keywords: Ant-CCP; Arthritis; Rheumatoid Arthritis