Increased Level Of Il-34 In Serum And Synovial Fluid Is Associated With Rheumatoid Factor And Anti-Cyclic Citrullinated Peptide Antibodies Titer In Patients With Rheumatoid Arthritis

Background Interleukin-34 (IL-34) is a recently discovered cytokine that binds macrophage colony-stimulating factor (M-CSF). Rheumatoid arthritis (RA) is a representative inflammatory arthritis characterized by increased osteoclastogenesis, which contributes to joint destruction and generalized bone loss. Objectives To identify the possible pathophysiological significance of IL-34 in RA, the level of this cytokine was measured in serum and synovial fluid (SF) from patients with RA. Methods IL-34 levels were measured in serum from 113 patients with RA, 56 patients with osteoarthritis (OA), and 36 controls, and in SF isolated from patients with RA ( n = 36) or OA ( n = 24). Correlations between serum IL-34 concentration and clinical and laboratory features, RA disease activity score, and bone mineral density (BMD) were assessed in RA patients. The levels of IL-1β, IL-6, IL-17α, interferon-γ-induced protein 10 (IP-10), receptor activator of nuclear factor kB ligand (RANKL), and dickkopf-1 (DKK-1), which are implicated in osteoclastogenesis, were also measured in serum and SF samples. Results RA patients had a significantly higher mean serum level of IL-34 than did OA patients and controls (188.0 ± 550.3, 36.6 ± 38.0, and 49.1 ± 78.5 pg/ml, respectively). Similarly, mean SF IL-34 concentration was also higher in RA than in OA patients. Paired samples isolated from seven RA patients showed similar levels of IL-34 in serum and SF. In serum from RA and OA patients, IL-34 levels were positively associated with IL-6 levels. SF IL-34 concentration correlated significantly with IL-6 (r = 0.482) and RANKL (r = 0.635) levels in RA but not in OA patients. In RA patients, serum IL-34 level did not correlate significantly with variables reflecting inflammation status, joint damage severity, or BMD. However, in RA patients, serum IL-34 level correlated significantly with rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibody titers (r = 0.282 and 0.491, respectively). Conclusions This study shows for the first time increased IL-34 concentrations in serum and SF in RA patients compared with OA patients and controls. Circulating IL-34 level is significantly associated with RF and anti-CCP antibody titers. These observations suggest a link between IL-34 and RA pathogenesis. References Lin H et al. Discovery of a cytokine and its receptor by functional screening of the extracellular proteome. Science (New York, NY) 2008; 320:807-811. Chen Z et al. The critical role of IL-34 in osteoclastogenesis. PloS one 2011; 6: e18689. Acknowledgements This research was partially supported by grants from Daewoong Pharmaceuticals Corporations. Disclosure of Interest None Declared