title: The acute-phase response is not predictive for the development of arthritis in seropositive arthralgia - a prospective cohort study.
abstract: OBJECTIVE
  To evaluate whether markers of the acute-phase response in patients presenting with arthralgia and positive anticitrullinated protein antibodies (ACPA) and/or immunoglobulin M rheumatoid factor (IgM-RF) could be predictive for the development of arthritis.
  
  
  METHODS
  In total, 137 ACPA- and/or IgM-RF-positive patients were included. Patients were followed annually for the development of arthritis, defined as presence of 1 or more swollen joints at clinical examination. High-sensitivity C-reactive protein (hsCRP), procalcitonin (PCT), secretory phospholipase A2 (SPLA2), tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), IL-12p70, IL-10, and interferon-γ (IFN-γ) were measured in baseline serum samples. Gene expression focusing on a predefined panel of genes coding for inflammatory molecules was measured by multiplex ligation-dependent probe amplification.
  
  
  RESULTS
  Thirty-five patients (26%) developed arthritis within a median time of 11 months (interquartile range 3.7-18 mo). Circulating levels of cytokines, SPLA2, hsCRP, and PCT were not different between patients with progression to clinical arthritis and those without progression. However, a trend for IL-12p70, TNF-α, IL-10, IL-6, and SPLA2 was observed. No correlation between messenger RNA (mRNA) expression levels of inflammatory genes and progression to arthritis was found. Subgroup analysis of patients with early progression to arthritis showed higher levels of mRNA expression of poly(A)-specific ribonuclease and polycomb complex protein BMI-1 compared to patients without progression to arthritis.
  
  
  CONCLUSIONS
  Although low-grade inflammation is present before onset of clinical arthritis in large cohorts and can be detected using consecutive measurements, a single measurement of acute-phase reactants seems to have limited value for prediction of development of arthritis in individual patients.
authors.affiliation: Department of Internal Medicine, Slotervaart Hospital, Amsterdam, The Netherlands. maarten.limper@slz.nl
authors.forename: Maarten
authors.initials: M
authors.lastname: Limper
authors.forename: Lotte
authors.initials: L
authors.lastname: van de Stadt
authors.forename: Wouter
authors.initials: W
authors.lastname: Bos
authors.forename: Martijn
authors.initials: M
authors.lastname: de Kruif
authors.forename: Arnold
authors.initials: A
authors.lastname: Spek
authors.forename: Gertjan
authors.initials: G
authors.lastname: Wolbink
authors.forename: Dirkjan
authors.initials: D
authors.lastname: van Schaardenburg
authors.forename: Eric
authors.initials: E
authors.lastname: van Gorp
mesh_terms: D000210:Acute-Phase Reaction / Q000097:blood / Q000150:complications* / Q000276:immunology; D000328:Adult; D018771:Arthralgia / Q000097:blood / Q000150:complications* / Q000276:immunology; D001168:Arthritis / Q000097:blood / Q000209:etiology* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein; D002116:Calcitonin / Q000097:blood; D015740:Calcitonin Gene-Related Peptide; D016207:Cytokines / Q000097:blood; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D054467:Phospholipases A2 / Q000097:blood; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011498:Protein Precursors / Q000097:blood
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; C000606589:CALCA protein, human; D016207:Cytokines; D011498:Protein Precursors; D002116:Calcitonin; D002097:C-Reactive Protein; D054467:Phospholipases A2; D015740:Calcitonin Gene-Related Peptide