title: Simultaneous development of acute phase response and autoantibodies in preclinical rheumatoid arthritis.
abstract: OBJECTIVE
  To investigate the temporal relationship between onset of inflammation (as measured by secretory phospholipase A2 (sPLA2) and C reactive protein (CRP)) and the presence of autoantibodies (IgM rheumatoid factor (IgM RF) and antibodies against citrullinated peptides (anti-CCP)) in the preclinical phase of rheumatoid arthritis (RA).
  
  
  METHODS
  For 79 patients with RA who had been blood donors before the onset of disease, a median of 13 serum samples per patient was available. sPLA2 was measured in patient and matched control samples and related to previous CRP, IgM RF, and anti-CCP measurements. The temporal relationship between the increased markers of inflammation and autoantibodies was analysed with time lag analysis.
  
  
  RESULTS
  IgM RF and anti-CCP concentrations were significantly associated (p<0.001) with concentrations of sPLA2, CRP, and the combination of sPLA2 and CRP at the same time point. However, we found no stronger association between the two autoantibody tests and the three inflammation measures 1, 2, and 3 years before or after a time point than for measurements at the same time, in the whole group or in subgroups of IgM RF and anti-CCP positive patients.
  
  
  CONCLUSIONS
  Both the acute phase response and autoantibody formation often develop years before the first symptoms of RA occur, and these phenomena are probably closely connected in time.
authors.affiliation: Jan van Breemen Institute, Amsterdam, The Netherlands.
authors.forename: M M J
authors.initials: MM
authors.lastname: Nielen
authors.forename: D
authors.initials: D
authors.lastname: van Schaardenburg
authors.forename: H W
authors.initials: HW
authors.lastname: Reesink
authors.forename: J W R
authors.initials: JW
authors.lastname: Twisk
authors.forename: R J
authors.initials: RJ
authors.lastname: van de Stadt
authors.forename: I E
authors.initials: IE
authors.lastname: van der Horst-Bruinsma
authors.forename: M H M T
authors.initials: MH
authors.lastname: de Koning
authors.forename: M R
authors.initials: MR
authors.lastname: Habibuw
authors.forename: B A C
authors.initials: BA
authors.lastname: Dijkmans
mesh_terms: D000210:Acute-Phase Reaction / Q000097:blood / Q000209:etiology* / Q000276:immunology; D017668:Age of Onset; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000150:complications* / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology; D010741:Phospholipases A / Q000097:blood; D054467:Phospholipases A2; D012217:Rheumatoid Factor / Q000097:blood
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D007075:Immunoglobulin M; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D002097:C-Reactive Protein; D012217:Rheumatoid Factor; D010741:Phospholipases A; D054467:Phospholipases A2