The Acute-phase Response Is Not Predictive for the Development of Arthritis in Seropositive Arthralgia - A Prospective Cohort Study

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. 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. 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. 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