title: Isotype distribution of anti-cyclic citrullinated peptide antibodies in undifferentiated arthritis and rheumatoid arthritis reflects an ongoing immune response.
abstract: OBJECTIVE
  The evolution of the rheumatoid arthritis (RA)-specific anti-cyclic citrullinated peptide (anti-CCP) antibody response, as measured by the isotypes of anti-CCP, has not been described. This study was undertaken to determine anti-CCP isotype usage in patients with undifferentiated arthritis (UA), patients with recent-onset RA, and patients with RA of long duration.
  
  
  METHODS
  IgA, IgM, and IgG subclasses of anti-CCP were measured by enzyme-linked immunosorbent assay in serum samples that were obtained from IgG anti-CCP antibody-positive patients with UA (n = 110) and IgG anti-CCP antibody-positive patients with RA (n = 152) early after the onset of arthritis. Patients with UA in whom RA developed within 1 year (UA-->RA) were compared with patients with UA in whom RA did not develop within 1 year (UA-->UA). In addition, baseline serum samples obtained from a subset of patients with RA (n = 64) were compared with sera obtained from the same patients a median of 7 years later.
  
  
  RESULTS
  IgM anti-CCP was present in early samples from both patients with UA and patients with RA and in followup samples from patients with RA. Several IgG anti-CCP antibody-positive patients who did not have IgM anti-CCP early after disease onset did display IgM anti-CCP later in the course of the arthritis. A diverse pattern of isotype usage was detected in early samples, with a trend toward lower frequencies of all isotypes of anti-CCP in patients with UA compared with patients with RA and in UA-->UA patients compared with UA-->RA patients. Levels of all isotypes except IgG1 had decreased after 7 years.
  
  
  CONCLUSIONS
  These data indicate development of the anti-CCP isotype repertoire into full usage early in the course of arthritis. The sustained presence of IgM anti-CCP indicates ongoing recruitment of new B cells into the anti-CCP response, reflecting a continuous (re)activation of the RA-specific anti-CCP response during the course of anti-CCP-positive arthritis.
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands. K.N.Verpoort@lumc.nl
authors.forename: K N
authors.initials: KN
authors.lastname: Verpoort
authors.forename: C M
authors.initials: CM
authors.lastname: Jol-van der Zijde
authors.forename: E A M
authors.initials: EA
authors.lastname: Papendrecht-van der Voort
authors.forename: A
authors.initials: A
authors.lastname: Ioan-Facsinay
authors.forename: J W
authors.initials: JW
authors.lastname: Drijfhout
authors.forename: M J D
authors.initials: MJ
authors.lastname: van Tol
authors.forename: F C
authors.initials: FC
authors.lastname: Breedveld
authors.forename: T W J
authors.initials: TW
authors.lastname: Huizinga
authors.forename: R E M
authors.initials: RE
authors.lastname: Toes
mesh_terms: D000917:Antibody Formation; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D006801:Humans; D007132:Immunoglobulin Isotypes / Q000276:immunology*; D010456:Peptides, Cyclic / Q000276:immunology*; D013997:Time Factors
chemical_list: D001323:Autoantibodies; D007132:Immunoglobulin Isotypes; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide