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Prophylactic Injection of Recombinant Alpha-Enolase Reduces Arthritis Severity in the Collagen-Induced Arthritis Mice
Clément Guillou1, Céline Derambure1, Manuel Fréret1
1INSERM, U905, Rouen, France; Normandy University, Institute for Research and Innovation in Biomedicine (IRIB), Rouen, France.
Objective:
To evaluate the ability of the glycolytic enzyme alpha-enolase (ENO1) or its immunodominant peptide (pEP1) to reduce the severity of CIA in DBA/1 mice when injected in a prophylactic way.
Methods:
Mice were treated with mouse ENO1 or pEP1 one day prior to collagen II immunization. Clinical assessment was evaluated using 4 parameters (global and articular scores, ankle thickness and weight). Titers of serum anti-ENO1, anti-cyclic citrullinated peptides (anti-CCP) and anti-CII (total IgG and IgG1/IgG2a isotypes) antibodies were measured by ELISA at different time-points. Disease activity was assessed by histological analysis of both anterior and hind paws at the end of experimentation.
Results:
Prophylactic injection of 100 μg of ENO1 reduced severity of CIA. Serum levels of anti-CII antibodies were reduced in ENO1-treated mice. Concordantly, ENO1-treated mice joints presented less severe histological signs of arthritis. ENO1 did not induce a shift toward a Th2 response since IgG1/IgG2a ratio of anti-CII antibodies remained unchanged and IL-4 serum levels were similar to those measured in the control group.
Conclusions:
Pre-immunization with ENO1 or its immunodominant peptide pEP1 reduces CIA severity at the clinical, immunological and histological levels. Effects of pEP1 were less pronounced. This immunomodulatory effect is associated with a reduction in anti-CII antibodies production but is not due to a Th1/Th2 shift.
Insights
Prophylactic administration of alpha-enolase (ENO1) or its peptide (pEP1) reduced collagen-induced arthritis (CIA) severity in mice. This immunomodulatory effect lowered anti-collagen antibodies but did not involve a Th1/Th2 shift.
Area of Science:
- Immunology
- Rheumatology
- Biochemistry
Background:
- Collagen-induced arthritis (CIA) is a common animal model for rheumatoid arthritis.
- Alpha-enolase (ENO1) is a glycolytic enzyme with potential immunomodulatory roles.
- Understanding ENO1's role in autoimmune diseases is crucial for developing novel therapies.
Purpose of the Study:
- To investigate the prophylactic effect of ENO1 and its peptide pEP1 on CIA severity in DBA/1 mice.
- To assess the impact of ENO1 and pEP1 on clinical, immunological, and histological parameters of CIA.
- To determine the underlying immunological mechanisms, specifically the Th1/Th2 response.
Main Methods:
- DBA/1 mice were treated with ENO1 or pEP1 before collagen II immunization.
- Clinical arthritis was assessed using global and articular scores, and ankle thickness.
- Antibody titers (anti-ENO1, anti-CCP, anti-CII) and serum IL-4 levels were measured by ELISA.
- Histological analysis of paw joints evaluated disease severity.
Main Results:
- Prophylactic ENO1 injection significantly reduced CIA severity at clinical and histological levels.
- ENO1 treatment led to decreased serum levels of anti-collagen type II (anti-CII) antibodies.
- No significant shift towards a Th2 response was observed, as indicated by unchanged IgG1/IgG2a ratios and IL-4 levels.
Conclusions:
- Pre-immunization with ENO1 effectively mitigates CIA severity, impacting clinical, immunological, and histological outcomes.
- The immunomodulatory effect of ENO1 is linked to reduced anti-CII antibody production.
- The peptide pEP1 showed a less pronounced effect compared to full-length ENO1, and the mechanism does not involve a Th1/Th2 polarization.
