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Prophylactic injection of non-citrullinated α-enolase has immunomodulatory effects in collagen-induced arthritis mice
  1. C Guillou1,
  2. G Avenel2,
  3. C Derambure1,2,
  4. F Le Loarer3,
  5. M Verdet2,
  6. M Hiron1,
  7. M Maho1,2,
  8. X Le-Loet2,
  9. S Adriouch1,
  10. J C Sabourin3,
  11. O Boyer1,
  12. T Lequerre1,2,
  13. O Vittecoq1,2
  1. 1INSERM U905, Institue for Biomedical Research, University of Rouen, Rouen, France
  2. 2Department of Rheumatology, Rouen University Hospital, Rouen, France
  3. 3Laboratory of Histology, Rouen University Hospital, Rouen, France

Abstract

Background Identification of autoantibodies associated with rheumatoid arthritis (RA) has been of major interest. In this context, the authors 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, the authors have evaluated, in the well-known collagen induced arthritis model, the clinical, immunological and histological effects of both recombinant non-citrullinated α-enolase and immunodominant peptides from human and bacterial species.

Methods Different doses of α-enolase (10 and 100 µg) or immunodominant enolase peptide 1 from human (hEP1) or porphyromonas Gingivalis (pEP1) (10 or 100µg) were intraperitoneally injected to 6 week-old DBA/1 mice one day prior to collagen II arthritis induction (CIA). Both clinical (weight, arthritis score, tarsal thickness) and biological (anticollagen II and anti-α-enolase antibodies) were assessed during the 90 days follow-up period. Four histological score were also assessed: inflammation, syniovial thickening, cartilage resorption and bone resorption.

Results 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 anticollagen II antibodies were significantly lower whereas titers of anti-α-enolase antibodies were significantly higher in mice treated with 100 µg of α-enolase compared to control mice. Moreover, histological score were in agreement with clinical score. As regards to hEP1 and pEP1, the authors 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 suggest a protective role of this molecule. The clinical effect is not due to an imunological response mediated by anti-α-enolase antibodies. Prophylactic injection could induce either an immune deviation or an emergence of regulatory lymphocyte population, responsible of a decrease of anti-CII antibodies production. These results suggest α-enolase has an immunomodulatory effect in CIA mice. Those results suggest that non-citrullinated α-enolase could constitute a potential new therapeutic approach in RA.

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