A8.2 Anti Citrullinated Protein Antibodies from Synovial Fluid of Rheumatoid Arthritis Patients Enhance Osteoclastogenesis

Abstract

Background/Purpose Presence of anti CCP2 antibodies identifies a subgroup of RA patients that are more prone to develop bone erosions. We hypothesised that anti CCP2 IgG might have a direct effect on bone, and thus investigated the effect of anti CCP2 IgG isolated from synovial fluid (SF) of RA patients on osteoclastogenesis and bone destruction in an in vitro system. Methods IgG were isolated on Protein G columns from SF of 26 RA patients and applied on CCP2 affinity columns. Pools of the purified anti-CCP2 and flow through IgG fractions were tested for the ability to influence osteoclastogenesis (TRAP positive multinucleated cells) and bone destruction (% of resorption area on osteologic discs). To do this immature dendritic cells derived from CD14+ cells from peripheral blood of healthy individuals were cultured in the presence of RANKL and M-CSF, with or without CCP2 IgG or flow through IgG (at a final concentration of 100 ng/ml). Results The CCP2 IgG pool induced a significant mean ± SEM of 1.5 ± 0.1 fold increase in the number of osteoclasts formed from immature dendritic cells in the presence of RANKL, while no such effect was observed with flow through IgG fractions. Osteoclasts cultured in the presence of the CCP2 IgG induced a significant mean ± SEM of 3.4 ± 1.3 fold increase of bone resorption while no such effect was observed for the flow through fractions. Conclusions Here, we demonstrate that ACPA IgG, isolated from SF of RA patients, have the ability to enhance the RANKL-driven osteocalstogenesis from immature dendritic cells. Our findings suggest that ACPA might have a direct pathogenic effect in RA associated bone destruction.