Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.


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

Guillou1,  Clément, Avenel1,  Gilles, Derambure1,  Céline, Verdet1,  Mathieu, Hiron1,  Martine, Maho1,  Maude, Le Loet2,  Xavier

Inserm 905 & Institute for Biomedical Research, University of Rouen, Rouen, France
Department of Rheumatology, Rouen University Hospital & Inserm 905, Institute for Biomedical Research, University of Rouen, Rouen, France

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 a-enolase as a new auto-antigen in early RA*. Moreover, subsequent studies have shown that citrullination of a-enolase is crucial for its autoantigenicity. a-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 a-enolase and immunodominant peptides from human and bacterial species.

Methods:

Different doses of a-enolase (10 and 100 mg) or immunodominant enolase peptide 1 from human [hEP1] or Porphyromonas gingivalis[pEP1] (1, 10 or 100mg) 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-a-enolase antibodies) were assessed during the 90 days follow-up period.

Results:

Prophylactic injection of recombinant a-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 mg led to better results. Levels of anti-collagen II antibodies were significantly lower whereas titers of anti-a-enolase antibodies were significantly higher in mice treated with 100 mg 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 a-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 a-enolase could constitute a potential new therapeutic approach in RA.

To cite this abstract, please use the following information:
Guillou, Clément, Avenel, Gilles, Derambure, Céline, Verdet, Mathieu, Hiron, Martine, Maho, Maude, et al; Prophylactic Injection of Non-Citrullinated Alpha-Enolase Has Immunomodulatory Effects in Collagen-Induced Arthritis Mice. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :2093
DOI:

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