2093 - Prophylactic Injection of Non-Citrullinated Alpha-Enolase Has Immunomodulatory Effects in Collagen-Induced Arthritis Mice. 

Tuesday, November 8, 2011: 9:00 AM-6:00 PM
Hall F2 - Poster Hall (McCormick Place West)
Clément Guillou1, Gilles Avenel1, Céline Derambure1, Mathieu Verdet1, Martine Hiron1, Maude Maho1, Xavier Le Loët2, Sahil Adriouch1, Olivier Boyer1, Thierry Lequerré2 and Olivier Vittecoq2, 1Inserm 905 & Institute for Biomedical Research, University of Rouen, Rouen, France, 2Department of Rheumatology, Rouen University Hospital & Inserm 905, Institute for Biomedical Research, University of Rouen, Rouen, France
Presentation Number: 2093

Background/Purpose: Identification of autoantibodies associated with rheumatoid arthritis (RA) has been of major interest. In this context, we have previously identified for the first time α-enolase as a new auto-antigen in early RA*. Moreover, subsequent studies have shown that citrullination of α-enolase is crucial for its autoantigenicity. α-enolase is an evolutionary conserved protein implicated both in glycolysis pathway and as a plasminogen receptor. Here, we have evaluated, in the well-known collagen induced arthritis (CIA) model, the clinical and immunological effects of both recombinant non-citrullinated α-enolase and immunodominant peptides from human and bacterial species.

Method: Different doses of α-enolase (10 and 100 µg) or immunodominant enolase peptide 1 from human [hEP1] or Porphyromonas gingivalis [pEP1] (1, 10 or 100µg) were intraperitoneally injected to 6 week-old DBA/1 mice one day prior to collagen II arthritis induction. Both clinical (weight, arthritis score, tarsal thickness) and biological (anti-collagen II and anti-α-enolase antibodies) were assessed during the 90 days follow-up period.

Result:Prophylactic injection of recombinant α-enolase was able to significantly prevent weight loss and to decrease the severity of arthritis evaluated by the arthritis score as well as the tarsal thickness. There was a dose-effect since 100 µg led to better results. Levels of anti-collagen II antibodies were significantly lower whereas titers of anti-α-enolase antibodies were significantly higher in mice treated with 100 µg of a-enolase compared to control mice. As regards to hEP1 and pEP1, we etablished a dose-dependant protective effect in CIA which is significant for pEP1. This protective effect is not due to once again a decrease of anti-collagen II antibodies titer.

Conclusion:Prophylactic treatment with recombinant α-enolase as well as immunodominant peptides has immunomodulatory effects in collagen-induced arthritis mice. The regulatory mechanisms induced by this protein seem to be partially due to a control of the production of anti-collagen II antibodies. Those results suggest that non-citrullinated α-enolase could constitute a potential new therapeutic approach in RA. 

Keywords: rheumatoid arthritis, pathogenesis

Disclosure: C. Guillou, None; G. Avenel, None; C. Derambure, None; M. Verdet, None; M. Hiron, None; M. Maho, None; X. Le Loët, None; S. Adriouch, None; O. Boyer, None; T. Lequerré, None; O. Vittecoq, None.