Treatment with Cl-amidine, a peptidyl arginine deiminase (PAD) inhibitor, significantly reduces collagen-induced arthritis (CIA) (50.6)

Abstract

Abstract Antibodies to citrullinated protein antigens (ACPA) are specific for rheumatoid arthritis (RA). Post-translational citrullination of epitopes to which ACPA are directed is catalyzed by PADs. We have previously shown that ACPA develop in CIA and contribute to joint damage. In this study we used Cl-amidine, a small molecule that specifically inhibits all PAD enzymes, to determine whether limiting PAD activity can modify CIA. CIA and collagen antibody-induced arthritis (CAIA, a model of the antibody-mediated effector pathway of CIA) were induced in DBA/1j mice using standard methods. Mice received either no treatment, vehicle alone (PBS), or 1, 10 or 50 mg/kg/day Cl-amidine by daily IP injection. Cl-amidine reduced CIA disease activity scores by 42%, 53% and 55% in the respective treatment groups (1, 10, 50 mg/kg/day) as well as C3 deposition, IgG1 and IgG2a anti-mouse CII Abs and epitope spreading to citrullinated epitopes. Conversely, Cl-amidine treatment had no effect on the development of CAIA. These results suggest that PADs are essential components in the development of inflammatory arthritis. This work was funded by an ACR REF WOR Grant.