title: The concentration of anticitrullinated protein antibodies in serum and synovial fluid in relation to total immunoglobulin concentrations.
abstract: BACKGROUND
  Anticitrullinated protein antibodies (ACPA) are one of the best predictors for the development of rheumatoid arthritis. Nonetheless, relatively little information is present on the absolute concentration of ACPA in relation to total immunoglobulin (Ig) concentrations. Such information would be of relevance to compare ACPA levels to other antibody levels. Here, we estimated the relative abundance of ACPA Ig in serum and synovial fluid using a quantitative approach.
  
  
  METHODS
  ACPA were purified using HiTrap Streptavidin columns coupled with biotinylated cyclic citrullinated peptide (CCP2). Total Ig and anti-CCP2 isotype reactivities were measured by ELISA.
  
  
  RESULTS
  ACPA were successfully isolated as substantial antibody amounts were eluted from sera of ACPA-positive patients and neglectable antibody amounts were eluted from sera of ACPA-negative patients. Up to 1 in 80 IgG-molecules were estimated to be ACPA. Strikingly, IgM-ACPA was most abundant in synovial fluid (with the highest enrichment in the range of one IgM-ACPA for every eight IgM-antibodies).
  
  
  CONCLUSIONS
  ACPA-IgG levels are estimated to be within the range of peak levels of protective antibody responses against recall antigens. IgM-ACPA is abundantly present in synovial fluid, suggesting the presence of a continuous ongoing autoimmune response in the synovial compartment.
authors.affiliation: Department of Rheumatology, Leiden University Medical Center (LUMC), Leiden, The Netherlands. a.willemze@lumc.nl
authors.forename: Annemiek
authors.initials: A
authors.lastname: Willemze
authors.forename: Jing
authors.initials: J
authors.lastname: Shi
authors.forename: Marlies
authors.initials: M
authors.lastname: Mulder
authors.forename: Gerrie
authors.initials: G
authors.lastname: Stoeken-Rijsbergen
authors.forename: Jan W
authors.initials: JW
authors.lastname: Drijfhout
authors.forename: Tom W J
authors.initials: TW
authors.lastname: Huizinga
authors.forename: Leendert A
authors.initials: LA
authors.lastname: Trouw
authors.forename: Rene E M
authors.initials: RE
authors.lastname: Toes
mesh_terms: D001172:Arthritis, Rheumatoid / Q000097:blood / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D016022:Case-Control Studies; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007132:Immunoglobulin Isotypes / Q000097:blood / Q000276:immunology*; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D010456:Peptides, Cyclic / Q000276:immunology*; D013582:Synovial Fluid / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D007075:Immunoglobulin M; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide
keywords: Autoantibodies; Rheumatoid Arthritis; Synovial fluid