title: The role of anticitrullinated protein antibodies in the early stages of rheumatoid arthritis.
abstract: OBJECTIVE
  This review provides an update on the recent discoveries on the role of anticitrullinated protein antibodies (ACPA) in early rheumatoid arthritis (RA).
  
  
  RESULTS
  RA is characterized by an immune response against posttranslationally modified proteins, in particular citrullinated proteins. Recent studies have found that the ACPA response matures shortly before clinical disease manifests itself and is characterized by an increase in titre, isotype switching, antigen-recognition profile, and a change in the Fc-glycosylation pattern. To date, many citrullinated autoantigens have been identified and novel studies suggest that the human leucocyte antigen class II locus may directly influence the maturation of the ACPA response via antigen-specific T cells. Clinical studies have demonstrated that effective treatment of arthritis can lead to reduced ACPA levels or a change in composition of ACPA. In addition to ACPA, autoantibodies targeting other posttranslational modifications have been identified and may be associated with disease prognosis.
  
  
  CONCLUSIONS
  Key studies have demonstrated that autoimmunity against citrullinated proteins is already present in preclinical RA and matures over time. Future studies are required to reveal whether autoantibodies and the B cells that produce them play a role in disease development or can function as biomarkers for disease maturation.
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Dekkers
authors.forename: René E M
authors.initials: RE
authors.lastname: Toes
authors.forename: Tom W J
authors.initials: TW
authors.lastname: Huizinga
authors.forename: Diane
authors.initials: D
authors.lastname: van der Woude
mesh_terms: D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D015551:Autoimmunity; D015415:Biomarkers / Q000378:metabolism; D006801:Humans; D011379:Prognosis
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D015415:Biomarkers