Citrullinated mouse collagen administered to DBA/1J mice in the absence of adjuvant initiates arthritis

Introduction: Citrullinated self-proteins are thought to be involved in the onset/progression of rheumatoid arthritis (RA). Numerous studies have been performed to look for the self-antigen that becomes citrullinated and induces RA. Importantly, these studies have been performed using citrullinated self-antigens injected into an animal model in the presence of a strong adjuvant in order to derive the response. However, to date no studies have been performed to determine if these phenotypes can be induced in the absence of an adjuvant. Methods: To investigate this possibility, mice were immunized with citrullinated or non-citrullinated mouse Type II collagen (Cit-Col or Col) in the presence or absence of Freund's Complete Adjuvant (FCA). Results: An autoimmune-like RA response was observed in mice immunized with Cit-Col in the absence of FCA: by the increase in caliper score, visual observation, and micro-CT analysis of bone erosions. Antibody and T-cell responses were increased in the Cit-Col injected mice to Cit-Col as well as antibody to Anti-Citrullinated Peptide Antigens (ACPA) as determined by a commercially available test kit. Conclusions: Therefore, the use of citrullinated mouse collagen induces an autoimmune-like RA in the absence of an adjuvant. These data also suggest that citrullinate self-proteins may be potential molecular adjuvants that assist in driving an inflammatory response, that increases the production of PAD in joint tissue, resulting in the citrullination of other self-proteins to exacerbate the disease. (C) 2012 Elsevier B.V. All rights reserved.